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Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes
1Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Abstract:
Effects of Co2+ on the delayed outward K+ current (IK) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. IK was activated by depolarizing voltage pulses positive to -30 mV and reached half-maximal activation at +24 mV. Co2+ shifted the activation curve to a more depolarized voltage range in a concentration-dependent manner, with a Co2+ concentration at which half-maximal response occurs (IC50) of 8 mM and a saturation value of +38 mV. The voltage dependency of IK gatings showed a shift similar to that of activation. In both cases the shift could be explained by screening of surface potential. The density of total negative surface charges sensed by Co2+ was estimated to be 1 e/225 A2. Co2+ also reduced the fully activated IK [IK(full)], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of IK(full) was mainly voltage independent. The single-channel unitary current estimated by fluctuation analysis was approximately 0.1 pA at -30 mV either in the absence or presence of Co2+. Therefore, the depression of IK(full) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed IK through multiple mechanisms.
Insights
Cobalt ions (Co2+) affect potassium currents (IK) in guinea pig heart cells. Co2+ alters IK activation and reduces its overall function by affecting channel availability.
Area of Science:
- Cardiovascular Physiology
- Ion Channel Electrophysiology
- Pharmacology
Background:
- Delayed outward potassium current (IK) is crucial for cardiac repolarization.
- Understanding ion channel modulation is key to cardiac function.
- Cobalt ions (Co2+) are known modulators of ion channels.
Purpose of the Study:
- To investigate the effects of Co2+ on IK in guinea pig ventricular myocytes.
- To elucidate the mechanisms by which Co2+ influences IK.
Main Methods:
- Whole-cell patch-clamp technique.
- Voltage-clamp analysis of IK activation and gating.
- Fluctuation analysis for single-channel current estimation.
Main Results:
- Co2+ shifted IK activation and gating to more depolarized potentials, suggesting surface charge screening.
- Co2+ reduced fully activated IK (IK(full)) in a voltage-independent manner.
- Co2+ decreased the number of functional IK channels without altering single-channel current.
Conclusions:
- Co2+ depresses cardiac IK through multiple mechanisms.
- Surface charge screening and reduction in functional channel number are key effects of Co2+.
- These findings contribute to understanding cardiac electrophysiology modulation.
