Characterization of large conductance Ca2+-activated K+ channels in cerebellar Purkinje neurons

Mary D. Womack, Kamran Khodakhah

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

We investigated the role of large conductance, calcium-activated potassium channels (BK channels) in regulation of the excitability of cerebellar Purkinje neurons. Block of BK channels by iberiotoxin reduced the afterhyperpolarization of spontaneous action potentials in Purkinje neurons in acutely prepared cerebellar slices. To establish the conditions required for activation of BK channels in Purkinje neurons, the dependence of BK channel open probability on calcium concentration and membrane voltage were investigated in excised patches from soma of acutely prepared Purkinje cells. Single channel currents were studied under conditions designed to select for potassium currents and in which voltage-activated currents were largely inactivated. Micromolar calcium concentrations activated channels with a mean single channel conductance of 266 pS. BK channels were activated by both calcium and membrane depolarization, and showed no sign of inactivation. At a given calcium concentration, depolarization over a 60-mV range increased the mean open probability (PO) from <0.1 to >0.8. Increasing the calcium concentration shifted the voltage required for half maximal activation to more hyperpolarized potentials. The apparent affinity of the channels for calcium increased with depolarization. At -60 mV the apparent affinity was ≈35 μM decreasing to ≈3 μM at +40 mV. These results suggest that BK channels are unlikely to be activated at resting membrane potentials and calcium concentrations. We tested the hypothesis that Purkinje cell BK channels may be activated by calcium entry during individual action potentials. Significant BK channel activation could be detected when brief action potential-like depolarizations were applied to patches under conditions in which the sole source of calcium was flux across the plasma membrane via the endogenous voltage-gated calcium channels. It is proposed that BK channels regulate the excitability of Purkinje cells by contributing to afterhyperpolarizations and perhaps by shaping individual action potentials.

Original languageEnglish (US)
Pages (from-to)1214-1222
Number of pages9
JournalEuropean Journal of Neuroscience
Volume16
Issue number7
DOIs
StatePublished - 2002

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels
Purkinje Cells
Calcium
Action Potentials
Calcium Channels
Membranes
Carisoprodol
Membrane Potentials
Potassium
Cell Membrane

Keywords

  • BK channels
  • Excitability
  • Motor coordination
  • Mouse
  • Spontaneous firing

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Characterization of large conductance Ca2+-activated K+ channels in cerebellar Purkinje neurons. / Womack, Mary D.; Khodakhah, Kamran.

In: European Journal of Neuroscience, Vol. 16, No. 7, 2002, p. 1214-1222.

Research output: Contribution to journalArticle

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