Isolation and characterization of I(Kr) in cardiac myocytes by Cs+ permeation.
- Shetuan Zhang
- American journal of physiology. Heart and…
We investigated the effect of external cations on the permeability characteristics and gating kinetics of the human ether-à-go-go-related gene (HERG) current using the whole-cell patch-clamp technique. Inward HERG currents were recorded on hyperpolarization in 140 mM external Cs+ and Rb+, as well as K+. The permeability ratios of Rb+ and Cs+ relative to K+ were 1.25 and 0.56, respectively. Biphasic outward currents were recorded on depolarization in 140 mM Cs+ and in Rb+ with much smaller amplitude. The voltage dependence of inactivation was affected by external cations, such that the half-inactivation voltage shifted from −69.4±3.7 mV in K+ to −30.7±1.6 mV in Cs+ and to −35.8±1.9 mV in Rb+ (n=5). The time constants of inactivation were also changed significantly by external cations; τ of inactivation at +40 mV was 16.4±2.2 ms in 140 mM K+, 181±20.3 ms in Cs+, and 94.1±7.6 ms in Rb+ (n=5). Voltage dependence of activation was not altered significantly. The inhibition of the rapid inactivation mechanism by large cations may suggest that the “foot-in-the-door” model of gating is involved in HERG channel inactivation.