Two delayed rectifiers in guinea pig ventricular myocytes distinguished by tail current kinetics.

The delayed rectifier potassium current was studied in single guinea pig ventricular myocytes using the whole cell voltage clamp technique. Previous pharmacologic data indicated that the delayed rectifier in this preparation was a composite of two channel types (Sanguinetti and Jurkiewicz, 1990a; Balser et al., 1990). In guinea pig, the delayed rectifier tail current can be fit by the sum of two exponential functions having fast (approximately 125 ms) and slow (approximately 750 ms) decay time constants. The new findings here are as follows: 1) the fast decay phase derives solely from a channel type separable by voltage pulse protocol and the benzenesulfonamide agent, E-4031. In response to pulses of increasing duration, the fast phase amplitude increased to a plateau within 0.5 sec, whereas the slow phase required 3 to 6 sec. 5 microM E-4031 completely blocked the fast phase. 2) Whereas the drug-insensitive current contained only a slow decay phase, the drug-sensitive tail current contained a slow phase in addition to a fast decay phase. Both phases increased in amplitude in parallel with the drug-sensitive time-dependent current, indicating the existence of only one drug-sensitive channel. These pharmacologic and physiologic data will help define the characteristics of drug-sensitive and -insensitive currents. Furthermore, they indicate that the fast phase of tail current decay observed in the absence of drug represents a distinct channel type.