Voltage-dependent potassium currents in feline sino-atrial node myocytes

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We characterized the properties of the voltage-dependent K(+) currents I (to), I (Kr), and I (Ks) in isolated feline sino-atrial node (SAN) myocytes. I (to) activated rapidly and then inactivated with a single exponential and voltage-independent time course. Recovery from inactivation of I (to) followed a single exponential time course with τ = 21.1 ± 2.5 ms, at -80 mV. Steady-state inactivation relationship showed a V½ of inactivation at -47.9 ± 2.3 mV. These biophysical properties are similar to the fast I (to) phenotype of other mammals. I (Kr) exhibited typical negative slope conductance at test potentials > 0 mV and slow deactivation. I (Ks) activated very slowly. The functional contribution of I (to), I (Kr), and I (Ks) to the sustained pacemaking activity of feline SAN myocytes was analyzed. Similar to other mammals, I (to) underlies the initial repolarization phase of the SAN action potential, whereas I (Kr) and I (Ks) mediate repolarization back to the maximal diastolic potential. I (Kr) and I (Ks) also contribute to diastolic depolarization because of their slow deactivation kinetics. The I (Kr) specific blocker E-4031 and the I (Ks) blocker HMR 1556 significantly increased action potential duration, but had negligible effects on the maximum diastolic potential and only modest effects on the frequency of spontaneous activity, suggesting that each one of these two currents itself is capable of supporting action potential repolarization in the feline sinus node.