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.
Department of Internal Medicine, Section of Human Physiology, University of Perugia, I-06126 Italy.
Tiziana
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Sacco
Filippo
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Tempia
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