Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization.
1. Depolarizing pulses positive to 0 mV elicit a transient outward current (Ito) and a sustained 'pedestal' current in canine atrial myocytes. The pedestal current was highly sensitive to 4-aminopyridine (4-AP) and TEA, with 50% inhibitory concentrations (EC50) of 5.3 +/- 0.7 and 307 +/- 25 microM, respectively. When the pedestal current was separated from Ito with prepulses or by studying current sensitive to 10 mM TEA, it showed very rapid activation and deactivation. We therefore designated the current IKur,d, for 'ultrarapid delayed rectifier, dog'. IKur,d inactivation was bi-exponential, with mean time constants of 609 +/- 91 and 5563 +/- 676 ms during a 20 s pulse to +40 mV. 2. The reversal potential of IKur,d tail currents are dependent on extracellular potassium concentration ([K+]o; slope, 54.7 mV decade-1). The envelope of tails test was satisfied and the current inwardly rectified at > or = +40 mV. The current was insensitive to E-4031, dendrotoxin and chloride substitution, but was inhibited by barium, with an EC50 of 1.65 mM. Lanthanum ions caused a positive shift in voltage dependence without producing direct inhibition. 3. Single-channel activity was observed in cell-attached, inside-out and outside-out patches. Upon depolarization from -50 to +30 mV, single channels had similar time constants and [K+]o dependence to whole-cell current. Channel open probability (Po) increased with depolarization in a saturable fashion and the Po-voltage relation had a half-activation voltage and slope factor similar to whole-cell IKur,d. 4. Unitary channel current was linearly related to depolarization potential to +40 mV; at more positive potentials, inward rectification occurred. The unitary conductance was 20.3 and 35.5 pS for an [K+]o of 5.4 and 130 mM, respectively. Single-channel activity was strongly inhibited by 50 microM 4-AP or 10 mM TEA. Both 4-AP and TEA decreased open time, suggesting open-channel block. 5. Selective inhibition of IKur,d with 50 microM 4-AP or 0.3-5 mM TEA prolonged canine atrial action potentials, indicating that IKur,d contributes to canine atrial repolarization. The single-channel and macroscopic properties of IKur,d have many similarities to those of currents carried by Kv3.1 cloned channels and our findings thus suggest a possible role for Kv3.1 channels in cardiac repolarization.
Yue
L
L
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Feng
J
J
Li
G R
GR
Nattel
S
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D005260:Female; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011336:Probability; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011188:Potassium