Human ether-à-go-go-related gene K+ channel gating probed with extracellular ca2+. Evidence for two distinct voltage sensors.
J Gen Physiol
; 113(4): 565-80, 1999 Apr.
Article
in En
| MEDLINE
| ID: mdl-10102937
ABSTRACT
Human ether-à-go-go-related gene (HERG) encoded K+ channels were expressed in Chinese hamster ovary (CHO-K1) cells and studied by whole-cell voltage clamp in the presence of varied extracellular Ca2+ concentrations and physiological external K+. Elevation of external Ca2+ from 1.8 to 10 mM resulted in a reduction of whole-cell K+ current amplitude, slowed activation kinetics, and an increased rate of deactivation. The midpoint of the voltage dependence of activation was also shifted +22.3 +/- 2.5 mV to more depolarized potentials. In contrast, the kinetics and voltage dependence of channel inactivation were hardly affected by increased extracellular Ca2+. Neither Ca2+ screening of diffuse membrane surface charges nor open channel block could explain these changes. However, selective changes in the voltage-dependent activation, but not inactivation gating, account for the effects of Ca2+ on Human ether-à-go-go-related gene current amplitude and kinetics. The differential effects of extracellular Ca2+ on the activation and inactivation gating indicate that these processes have distinct voltage-sensing mechanisms. Thus, Ca2+ appears to directly interact with externally accessible channel residues to alter the membrane potential detected by the activation voltage sensor, yet Ca2+ binding to this site is ineffective in modifying the inactivation gating machinery.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Potassium Channels
/
Ion Channel Gating
/
Trans-Activators
/
Calcium
/
Potassium Channels, Voltage-Gated
/
Cation Transport Proteins
/
DNA-Binding Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
J Gen Physiol
Year:
1999
Document type:
Article
Affiliation country:
United States