A-type potassium currents active at subthreshold potentials in mouse cerebellar Purkinje cells.
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.
Sacco
Tiziana
T
Department of Internal Medicine, Section of Human Physiology, University of Perugia, I-06126 Italy.
Tempia
Filippo
F
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C087603:agitoxin 2; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005424:Flecainide; D011188:Potassium