[SHORT REPORTS] Voltage-Dependent Block of the Delayed Rectifier K^+ Current Induced by MS-551 in Single Rabbit Ventricular Myocytes

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The voltage-dependent block and recovery on the delayed rectifier potassium current (I_k) using MS-551 was investigated in single rabbit ventricular myocytes. Envelopes of tail currents were measured from two different holding potensials of -50 mV and -75mV. At -50 mV, the intensity of the block on the tail current induced by MS-551 at 3 μM was similar for all tested durations of the depolarizing pulse ranging from 50 msec to 3000 msed. At -75 mV, however, the intensity of the block progressively increased as the duration of the depolarizing pulse was prolonged, and reached steady state after several hundred msec of pulse. Recovery from the block was different for -75 mV and -50 mV, recovery was rapid with a time constant of 577 msec (n=6). At -50mV, however, recovery was barely detectable. These findings suggest that blocking I_k by MS-551 is enhanced at depolarizing membrane potentials, and that recovery occurs through the hyperpolarizing potentials. This voltage-dependent action of MS-551 on I_k may explain the use-dependent prolongation commonly associated with the action potential duration.
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