Bruce Bean, Ph.D.

Robert Winthrop Professor of Neurobiology
  • 617/432-1139

Our research is directed at understanding electrical signaling in the brain. Information in the brain is encoded as patterns of "action potentials", brief (~ 1 millsecond) reversals of the voltage across the membrane of neurons. Different neurons in the brain fire action potentials with a wide variety of distinct patterns. We seek to understand the different patterns of firing in terms of the underlying molecular devices - tiny pores in the membrane known as ion channels. In mammalian brains, each neuron possesses several dozen different types of ion channels. Most of these are closed when the neuron is at rest (electrically silent), and it is the coordinated, transient opening ("gating") of particular types of ion channels that underlies electrical signaling.

To understand how different combinations of ion channels work together to generate the distinct patterns of action potential firing in different neurons, we make electrical recordings from individual neurons using the patch clamp technique, either from neurons in brain slice preparations or from isolated neurons prepared using mild enzymatic treatment and mechanical dissociation. Gating of particular types of ion channels can be characterized at a sub-millisecond timescale using voltage clamp recordings, with components of electrical current carried by different types of ion channels separated using selective drugs or changes in the ionic composition of extracellular or intracellular solutions.

Current projects are focused on understanding the mechanism by which some neurons can generate spontaneous electrical activity ("pacemaking"). These include studies on dopamine-secreting neurons in the midbrain that are part of the reward system and studies of particular classes of GABA-secreting neurons in the cerebral cortex and the cerebellum that are unusual for their ability to generate ultra-rapid electrical signaling.

We are also interested in the pharmacology of ion channels. Many clinically-used pharmacological agents, including antiepileptic drugs, interact with voltage-dependent channels. We are exploring how antiepileptic drugs can prevent abnormal firing patterns in cortical circuits without disrupting normal firing, with the goal of improving antiepileptic activity while minimizing side effects. In collaboration with Clifford Woolf at the Massachusetts General Hospital, we are also developing novel treatments for pain based on introducing charged derivatives of local anesthetics like lidocaine through the pore of TRPV1 channels, which are selectively expressed on pain-sensing neurons. This allows long-lasting inhibition of pain sensing fibers with no effect on motor fibers or sympathetic fibers and should be an improved method of local anesthesia.

Flow of current through sodium-selective (red) and calcium-selective (blue) ion channels in between (left) and during (right) spontaneous action potentials formed by dopamine-secreting cells in the substantia nigra pars compacta. Electrical current carried by calcium ions generates the spontaneous activity, and massive amounts of calcium also enter during the action potential. The calcium entry may help make the neurons susceptible to cell death in Parkinson's disease.

 
 

Electrical current carried by calcium ions generates the spontaneous activity, and massive amounts of calcium also enter during the action potential. The calcium entry may help make the neurons susceptible to cell death in Parkinson's disease.

  1. Kimm T, Bean BP. Inhibition of A-Type Potassium Current by the Peptide Toxin SNX-482. July 9, 2014. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  2. Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. April 3, 2014. Cell reports.

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  3. Liu PW, Bean BP. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons. April 2, 2014. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  4. Brenneis C, Kistner K, Puopolo M, Jo S, Roberson D, Sisignano M, Segal D, Cobos EJ, Wainger BJ, Labocha S, Ferreirós N, von Hehn C, Tran J, Geisslinger G, Reeh PW, Bean BP, Woolf CJ. Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block. January 1, 2014. British journal of pharmacology.

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  5. Jo S, Bean BP. Sidedness of carbamazepine accessibility to voltage-gated sodium channels. December 6, 2013. Molecular pharmacology.

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  6. Yamada-Hanff J, Bean BP. Persistent sodium current drives conditional pacemaking in CA1 pyramidal neurons under muscarinic stimulation. September 18, 2013. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  7. Roberson DP, Gudes S, Sprague JM, Patoski HA, Robson VK, Blasl F, Duan B, Oh SB, Bean BP, Ma Q, Binshtok AM, Woolf CJ. Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons. May 19, 2013. Nature neuroscience.

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  8. Puopolo M, Binshtok AM, Yao GL, Oh SB, Woolf CJ, Bean BP. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. January 9, 2013. Journal of neurophysiology.

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  9. Brenneis C, Kistner K, Puopolo M, Segal D, Roberson D, Sisignano M, Labocha S, Ferreirós N, Strominger A, Cobos EJ, Ghasemlou N, Geisslinger G, Reeh PW, Bean BP, Woolf CJ. Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing. January 2, 2013. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  10. Carter BC, Giessel AJ, Sabatini BL, Bean BP. Transient sodium current at subthreshold voltages: activation by EPSP waveforms. September 20, 2012. Neuron.

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  11. Liu P, Jo S, Bean BP. Modulation of neuronal sodium channels by the sea anemone peptide BDS-I. March 21, 2012. Journal of neurophysiology.

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  12. Roberson DP, Binshtok AM, Blasl F, Bean BP, Woolf CJ. Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and review. September 1, 2011. British journal of pharmacology.

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  13. Bosmans F, Puopolo M, Martin-Eauclaire MF, Bean BP, Swartz KJ. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors. June 13, 2011. The Journal of general physiology.

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  14. Jo S, Bean BP. Inhibition of neuronal voltage-gated sodium channels by brilliant blue G. May 2, 2011. Molecular pharmacology.

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  15. Carter BC, Bean BP. Incomplete inactivation and rapid recovery of voltage-dependent sodium channels during high-frequency firing in cerebellar Purkinje neurons. December 15, 2010. Journal of neurophysiology.

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  16. Milescu LS, Bean BP, Smith JC. Isolation of somatic Na+ currents by selective inactivation of axonal channels with a voltage prepulse. June 2, 2010. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  17. Khaliq ZM, Bean BP. Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances. May 26, 2010. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  18. Kim HY, Kim K, Li HY, Chung G, Park CK, Kim JS, Jung SJ, Lee MK, Ahn DK, Hwang SJ, Kang Y, Binshtok AM, Bean BP, Woolf CJ, Oh SB. Selectively targeting pain in the trigeminal system. March 16, 2010. Pain.

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  19. Cannon SC, Bean BP. Sodium channels gone wild: resurgent current from neuronal and muscle channelopathies. December 28, 2009. The Journal of clinical investigation.

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  20. Carter BC, Bean BP. Sodium entry during action potentials of mammalian neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons. December 24, 2009. Neuron.

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  21. Binshtok AM, Gerner P, Oh SB, Puopolo M, Suzuki S, Roberson DP, Herbert T, Wang CF, Kim D, Chung G, Mitani AA, Wang GK, Bean BP, Woolf CJ. Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents. July 1, 2009. Anesthesiology.

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  22. Bean BP. Inhibition by an excitatory conductance: a paradox explained. May 1, 2009. Nature neuroscience.

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  23. Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ, Samad TA. Nociceptors are interleukin-1beta sensors. December 24, 2008. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  24. Gerner P, Binshtok AM, Wang CF, Hevelone ND, Bean BP, Woolf CJ, Wang GK. Capsaicin combined with local anesthetics preferentially prolongs sensory/nociceptive block in rat sciatic nerve. November 1, 2008. Anesthesiology.

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  25. Khaliq ZM, Bean BP. Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons. October 22, 2008. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  26. Binshtok AM, Bean BP, Woolf CJ. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. October 4, 2007. Nature.

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  27. Jackson AC, Bean BP. State-dependent enhancement of subthreshold A-type potassium current by 4-aminopyridine in tuberomammillary nucleus neurons. October 3, 2007. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  28. Bean BP. Neurophysiology: stressful pacemaking. June 28, 2007. Nature.

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  29. Bean BP. The action potential in mammalian central neurons. June 1, 2007. Nature reviews. Neuroscience.

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  30. Puopolo M, Raviola E, Bean BP. Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. January 17, 2007. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  31. Martina M, Metz AE, Bean BP. Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin. October 25, 2006. Journal of neurophysiology.

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  32. Puopolo M, Bean BP, Raviola E. Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb. July 20, 2005. Journal of neurophysiology.

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  33. Swensen AM, Bean BP. Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. April 6, 2005. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  34. Bean BP. The molecular machinery of resurgent sodium current revealed. January 20, 2005. Neuron.

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  35. McDonough SI, Mori Y, Bean BP. FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of effects on ionic current and gating current. October 22, 2004. Biophysical journal.

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  36. Jackson AC, Yao GL, Bean BP. Mechanism of spontaneous firing in dorsomedial suprachiasmatic nucleus neurons. September 15, 2004. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  37. Do MT, Bean BP. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. March 31, 2004. Journal of neurophysiology.

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  38. Blair NT, Bean BP. Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. November 12, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  39. Swensen AM, Bean BP. Ionic mechanisms of burst firing in dissociated Purkinje neurons. October 22, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  40. Do MT, Bean BP. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. July 3, 2003. Neuron.

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  41. Martina M, Yao GL, Bean BP. Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. July 2, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  42. Blair NT, Bean BP. Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. December 1, 2002. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  43. Mitterdorfer J, Bean BP. Potassium currents during the action potential of hippocampal CA3 neurons. December 1, 2002. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  44. McDonough SI, Boland LM, Mintz IM, Bean BP. Interactions among toxins that inhibit N-type and P-type calcium channels. April 1, 2002. The Journal of general physiology.

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  45. Taddese A, Bean BP. Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons. February 14, 2002. Neuron.

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  46. Raman IM, Bean BP. Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. February 1, 2001. Biophysical journal.

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  47. Bean BP. Modulating modulation. March 1, 2000. The Journal of general physiology.

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  48. Greif GJ, Sodickson DL, Bean BP, Neer EJ, Mende U. Altered regulation of potassium and calcium channels by GABA(B) and adenosine receptors in hippocampal neurons from mice lacking Galpha(o). February 1, 2000. Journal of neurophysiology.

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  49. Raman IM, Bean BP. Properties of sodium currents and action potential firing in isolated cerebellar Purkinje neurons. April 30, 1999. Annals of the New York Academy of Sciences.

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  50. Burgess DL, Biddlecome GH, McDonough SI, Diaz ME, Zilinski CA, Bean BP, Campbell KP, Noebels JL. beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. April 1, 1999. Molecular and cellular neurosciences.

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  51. Raman IM, Bean BP. Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. March 1, 1999. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  52. McDonough SI, Bean BP. Mibefradil inhibition of T-type calcium channels in cerebellar purkinje neurons. December 1, 1998. Molecular pharmacology.

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  53. Sodickson DL, Bean BP. Neurotransmitter activation of inwardly rectifying potassium current in dissociated hippocampal CA3 neurons: interactions among multiple receptors. October 15, 1998. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  54. Feigenspan A, Gustincich S, Bean BP, Raviola E. Spontaneous activity of solitary dopaminergic cells of the retina. September 1, 1998. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  55. Bean BP, McDonough SI. Two for T. May 1, 1998. Neuron.

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  56. McDonough SI, Lampe RA, Keith RA, Bean BP. Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA. December 1, 1997. Molecular pharmacology.

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  57. Raman IM, Sprunger LK, Meisler MH, Bean BP. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. October 1, 1997. Neuron.

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  58. Raman IM, Bean BP. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. June 15, 1997. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  59. McDonough SI, Mintz IM, Bean BP. Alteration of P-type calcium channel gating by the spider toxin omega-Aga-IVA. May 1, 1997. Biophysical journal.

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  60. Sodickson DL, Bean BP. GABAB receptor-activated inwardly rectifying potassium current in dissociated hippocampal CA3 neurons. October 15, 1996. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  61. McDonough SI, Swartz KJ, Mintz IM, Boland LM, Bean BP. Inhibition of calcium channels in rat central and peripheral neurons by omega-conotoxin MVIIC. April 15, 1996. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  62. Cardozo DL, Bean BP. Voltage-dependent calcium channels in rat midbrain dopamine neurons: modulation by dopamine and GABAB receptors. September 1, 1995. Journal of neurophysiology.

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  63. Kuo CC, Bean BP. Slow binding of phenytoin to inactivated sodium channels in rat hippocampal neurons. October 1, 1994. Molecular pharmacology.

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  64. Boland LM, Morrill JA, Bean BP. omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons. August 1, 1994. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  65. Kuo CC, Bean BP. Na+ channels must deactivate to recover from inactivation. April 1, 1994. Neuron.

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  66. Bean B. Taking the beta test. March 3, 1994. Nature.

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  67. Sah DW, Bean BP. Inhibition of P-type and N-type calcium channels by dopamine receptor antagonists. January 1, 1994. Molecular pharmacology.

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  68. Mintz IM, Bean BP. Block of calcium channels in rat neurons by synthetic omega-Aga-IVA. November 1, 1993. Neuropharmacology.

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  69. Adams ME, Mintz IM, Reily MD, Thanabal V, Bean BP. Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels. October 1, 1993. Molecular pharmacology.

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  70. Kuo CC, Bean BP. G-protein modulation of ion permeation through N-type calcium channels. September 16, 1993. Nature.

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  71. Mintz IM, Bean BP. GABAB receptor inhibition of P-type Ca2+ channels in central neurons. May 1, 1993. Neuron.

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  72. Boland LM, Bean BP. Modulation of N-type calcium channels in bullfrog sympathetic neurons by luteinizing hormone-releasing hormone: kinetics and voltage dependence. February 1, 1993. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  73. Swartz KJ, Merritt A, Bean BP, Lovinger DM. Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission. January 14, 1993. Nature.

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  74. Swartz KJ, Bean BP. Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic glutamate receptor. November 1, 1992. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  75. Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ. A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. July 1, 1992. Neuron.

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  76. Mintz IM, Adams ME, Bean BP. P-type calcium channels in rat central and peripheral neurons. July 1, 1992. Neuron.

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  77. Bean BP. Pharmacology and electrophysiology of ATP-activated ion channels. March 1, 1992. Trends in pharmacological sciences.

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  78. Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. P-type calcium channels blocked by the spider toxin omega-Aga-IVA. February 27, 1992. Nature.

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  79. Bean BP. Whole-cell recording of calcium channel currents. January 1, 1992. Methods in enzymology.

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  80. Mintz IM, Venema VJ, Adams ME, Bean BP. Inhibition of N- and L-type Ca2+ channels by the spider venom toxin omega-Aga-IIIA. August 1, 1991. Proceedings of the National Academy of Sciences of the United States of America.

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  81. Bean BP. Pharmacology of calcium channels in cardiac muscle, vascular muscle, and neurons. July 1, 1991. American journal of hypertension.

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  82. Regan LJ, Sah DW, Bean BP. Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin. February 1, 1991. Neuron.

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  83. Bean B. Calcium channels. Gating for the physiologist. November 15, 1990. Nature.

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  84. Friel DD, Bean BP. Dual control by ATP and acetylcholine of inwardly rectifying K+ channels in bovine atrial cells. March 1, 1990. Pflügers Archiv : European journal of physiology.

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  85. Bean BP, Friel DD. ATP-activated channels in excitable cells. January 1, 1990. Ion channels.

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  86. Bean BP. ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. January 1, 1990. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  87. Bean BP, Williams CA, Ceelen PW. ATP-activated channels in rat and bullfrog sensory neurons: current-voltage relation and single-channel behavior. January 1, 1990. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  88. Bean BP. Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. July 13, 1989. Nature.

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  89. Bean BP, Rios E. Nonlinear charge movement in mammalian cardiac ventricular cells. Components from Na and Ca channel gating. July 1, 1989. The Journal of general physiology.

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  90. Bean B. More than a Ca2+ channel? April 1, 1989. Trends in neurosciences.

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  91. Bean BP. Multiple types of calcium channels in heart muscle and neurons. Modulation by drugs and neurotransmitters. January 1, 1989. Annals of the New York Academy of Sciences.

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  92. Bean BP. Classes of calcium channels in vertebrate cells. January 1, 1989. Annual review of physiology.

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  93. Huettner JE, Bean BP. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. February 1, 1988. Proceedings of the National Academy of Sciences of the United States of America.

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  94. Friel DD, Bean BP. Two ATP-activated conductances in bullfrog atrial cells. January 1, 1988. The Journal of general physiology.

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  95. Triggle DJ, Lazdunski M, Bean BP. [Calcium channels and calcium antagonists]. December 1, 1986. Medizinische Monatsschrift für Pharmazeuten.

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  96. Bean BP, Sturek M, Puga A, Hermsmeyer K. Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs. August 1, 1986. Circulation research.

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  97. Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC. Mechanisms of calcium channel modulation by beta-adrenergic agents and dihydropyridine calcium agonists. July 1, 1986. Journal of molecular and cellular cardiology.

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  98. Bean BP. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. July 1, 1985. The Journal of general physiology.

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  99. Bean BP. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. October 1, 1984. Proceedings of the National Academy of Sciences of the United States of America.

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  100. Cohen CJ, Bean BP, Tsien RW. Maximal upstroke velocity as an index of available sodium conductance. Comparison of maximal upstroke velocity and voltage clamp measurements of sodium current in rabbit Purkinje fibers. June 1, 1984. Circulation research.

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  101. Bean BP, Nowycky MC, Tsien RW. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells. January 1, 1984. Nature.

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  102. Bean BP, Cohen CJ, Tsien RW. Lidocaine block of cardiac sodium channels. May 1, 1983. The Journal of general physiology.

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  103. Tsien RW, Bean BP, Hess P, Nowycky M. Calcium channels: mechanisms of beta-adrenergic modulation and ion permeation. January 1, 1983. Cold Spring Harbor symposia on quantitative biology.

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  104. Cohen CJ, Bean BP, Colatsky TJ, Tsien RW. Tetrodotoxin block of sodium channels in rabbit Purkinje fibers. Interactions between toxin binding and channel gating. October 1, 1981. The Journal of general physiology.

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  105. Bean BP. Sodium channel inactivation in the crayfish giant axon. Must channels open before inactivating? September 1, 1981. Biophysical journal.

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  106. Bean BP, Shrager P, Goldstein DA. Modification of sodium and potassium channel gating kinetics by ether and halothane. March 1, 1981. The Journal of general physiology.

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