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Cesium blockade of delayed outward currents and electrically induced pacemaker activity in mammalian ventricular
Abstract:
The effects of Cs+, 5-25 mM, were studied in cat and guinea pig papillary muscles using voltage clamp and current clamp techniques. In solutions containing normal K+, the major effects of Cs+ were depolarization of the resting potential and reduction of the delayed outward current (ixl) between -80 and -20 mV. Both inward and outward portions of the isochronal current voltage relation (l-s clamps) were reduced by extracellular Cs+. This resulted in a substantial reduction of inward rectification and, by subtraction from the normal I-V relationship, the definition of a Cs+-sensitive component of current. Under current clamp conditions, 5-10 mM Cs+ produced a dose-dependent slowing of repetitive firing induced by depolarization. At higher concentrations (25 mM) the resting potential was depolarized and repetitive activity could not be induced by further depolarization. However, release of hyperpolarizing pulses was followed by prolonged bursts of repetitive action potentials, suggesting partial reversal of blockade or participation of another pacemaker process. The experimental results and a numerical simulation show that under readily attainable conditions, reduction in an outward pacemaker current may slow pacemaker activity.
Insights
Cesium ions (Cs+) slow heart muscle cell firing by reducing outward currents. This research clarifies how Cs+ affects cardiac electrical activity and pacemaker function.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Cardiac muscle cells possess unique electrical properties crucial for heart rhythm.
- Cesium ions (Cs+) are known modulators of ion channels, but their specific effects on cardiac pacemaker currents require detailed investigation.
Purpose of the Study:
- To investigate the electrophysiological effects of cesium ions (Cs+) on cardiac papillary muscles.
- To elucidate the role of Cs+-sensitive currents in modulating cardiac electrical activity and pacemaker function.
Main Methods:
- Utilized voltage clamp and current clamp techniques in cat and guinea pig papillary muscles.
- Applied varying concentrations of extracellular Cs+ (5-25 mM) to assess dose-dependent effects.
- Performed numerical simulations to model the impact of Cs+ on ion currents and action potentials.
Main Results:
- Extracellular Cs+ depolarized the resting potential and reduced the delayed outward current (Ixl) between -80 and -20 mV.
- Cs+ significantly reduced inward rectification and identified a Cs+-sensitive current component.
- Dose-dependent slowing of repetitive firing was observed, with higher concentrations causing depolarization and altered responses to hyperpolarizing pulses.
Conclusions:
- Reduction of an outward pacemaker current by Cs+ can significantly slow cardiac pacemaker activity.
- Cesium ions offer a valuable tool for dissecting the components of cardiac ion currents and their roles in electrical activity.
- Findings suggest potential implications for understanding cardiac arrhythmias and developing targeted therapies.