A-type Potassium Currents Active at Subthreshold Potentials in Mouse Cerebellar Purkinje Cells

J Physiol. 2002 Sep 1;543(Pt 2):505-20. doi: 10.1113/jphysiol.2002.022525.

Abstract

Voltage-dependent and calcium-independent K+ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mM) application isolated an A-type K+ current (I(K(A))) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K+ current. The I(K(A)) activated at about -60 mV, had a V(0.5) of activation of -24.9 mV and a V(0.5) of inactivation of -69.2 mV. The deactivation time constant at -70 mV was 3.4 +/- 0.4 ms, while the activation time constant at +20 mV was 0.9 +/- 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 +/- 3.1 and 97.6 +/- 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4 %) and 962.3 ms (21.6 %). The I(K(A)) was blocked by 4-aminopyridine with an IC50 of 67.6 microM. Agitoxin-2 (2 nM) blocked 17.4 +/- 2.1 % of the I(K(A)). Flecainide completely blocked the I(K(A)) with a biphasic effect with IC50 values of 4.4 and 183.2 microM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 nM) nor by flecainide (3 microM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 microM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Dendrites / physiology
  • Female
  • Flecainide / pharmacology
  • Male
  • Mice
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / physiology*
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Scorpion Venoms / pharmacology
  • Tetraethylammonium / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Scorpion Venoms
  • agitoxin 2
  • Tetraethylammonium
  • 4-Aminopyridine
  • Flecainide
  • Potassium

Grant support