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Effects of caffeine on background potassium current in isolated guinea pig ventricular myocytes
1University Department of Pharmacology, Oxford, England.
Abstract:
We investigated effects of caffeine on inward rectifier potassium current (Ik1) in voltage-clamped ventricular cells by slow ramp depolarization (15 mV/s). Caffeine 10 mM applied in the solution bathing the cells consistently reduced the slope of the current-voltage (I-V) relation over the range of -80 to -40 mV. This effect of caffeine was not prevented by loading cells with BAPTA (1,2-bis(2-aminophenoxy) ethane N,N,N',N'-tetra-acetic acid) to suppress contraction. In the absence of caffeine, reducing extracellular potassium from 5.4 to 2.7 mM caused the expected shift of the reversal potential for current in the negative direction and increased rectification. In low potassium, 10 mM caffeine continued to reduce the slope of the I-V relation. When 2 mM barium was applied to suppress Ik1, any effects of 10 mM caffeine were slight or absent. The observations are consistent with a blocking action of caffeine on Ik1 in guinea pig ventricular myocytes.
Insights
Caffeine was found to reduce the inward rectifier potassium current (Ik1) in heart cells. This suggests caffeine may block Ik1 channels in guinea pig ventricular myocytes.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Inward rectifier potassium current (Ik1) is crucial for cardiac action potential.
- Caffeine's effects on Ik1 in ventricular cells require further elucidation.
Purpose of the Study:
- To investigate the impact of caffeine on Ik1 in guinea pig ventricular myocytes.
- To determine the mechanism of caffeine's action on Ik1.
Main Methods:
- Voltage-clamped guinea pig ventricular cells.
- Slow ramp depolarization (15 mV/s) to assess current-voltage (I-V) relationships.
- Application of caffeine (10 mM) and barium (2 mM).
- Manipulation of extracellular potassium concentrations.
Main Results:
- Caffeine (10 mM) reduced the slope of the I-V relation for Ik1.
- This effect persisted in low extracellular potassium and was not prevented by BAPTA.
- Barium, an Ik1 blocker, abolished caffeine's effect, indicating specificity.
Conclusions:
- Caffeine exerts a blocking action on Ik1 in guinea pig ventricular myocytes.
- The findings suggest a direct interaction between caffeine and Ik1 channels.
- This has implications for understanding caffeine's cardiac electrophysiological effects.
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