Time, voltage and ionic concentration dependence of rectification of h-erg expressed in Xenopus oocytes

The rapid delayed rectifier, I(Kr), is believed to have h-erg (human ether-a-go-go related gene) as its molecular basis. A recent study has shown that rectification of h-erg involves a rapid inactivation process that involves rapid closure of the external mouth of the pore or C-type inactivation. We measured the instantaneous current to voltage relationship for h-erg channels using: the saponin permeabilized variation of the cut-open oocyte clamp technique, In contrast to C-type inactivation in other voltage-gated K⁺ channels, the rate of inactivation was strongly voltage dependent at depolarized potentials. This voltage dependence could be modulated independently of activation by increasing [K⁺](o) from 2 to 98 mM. These results suggest that inactivation of h-erg has its own intrinsic voltage sensor.