Attenuation of extracellular potassium concentration effects on cardiac Kv4.3 gating, by conventional KChIP2 isoforms
Amadi, Chiemezie Chianotu
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Voltage gated potassium (Kv) channels underlie transient outward current, I to , which contributes to repolarization of ventricular action potential. The underlying channels are not fully understood. One I to phenotype, I to,fast is mediated by Kv4.2 and/or Kv4.3. However, neither Kv4.2 nor Kv4.3 expressed alone in Xenopus oocytes reproduce the gating kinetics of I to,fast . In particular, kinetics of inactivation and recovery are significantly different in native tissue. Thus, suggesting modulation by physiological factors. We investigated the biophysical mechanisms of extracellular potassium ion concentration ([K + ] o ) and intracellular K v Ch annel I nteracting P roteins (KChIPs) modulation of Kv4.3 gating. Two microelectrode voltage clamp analysis was conducted on Xenopus laevis oocytes coinjected with cRNAs of Kv4.3 alone (control), Kv4.3 + KChIP2b, and Kv4.3 + KChIP2d (1:1 molar ratios; all cRNA cloned from ferret heart). My results suggest that elevated [K + ] o promotes channel open state; KChIPs attenuate [K + ] o effects on Kv4.3 gating, and promote a non-inactivated closed state.