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Effects of Ca2+ and catecholamines on the guinea pig atrium action potential plateau
Abstract:
The activation process in isolated electrically driven guinea pig atria was studied by means of simultaneous microelectrode and tension recording. Reducing external calcium from 2.5 to 1.25 mM prolonged the plateau but further reduction of calcium shortened it. Progressively increasing doses of the calcium antagonist D600 (up to 1.4 micrometer), however, monotonically decreased plateau duration. Either protocol monotonically decreased steady-state tension, but with markedly different effects on the restitution relation. Epinephrine, and to a lesser extent isoproterenol, restored plateau duration after exposure to either a calcium-free or D600-containing solution, but only the isoproterenol effect was propranolol sensitive. Addition of calcium chelators enhanced rather than prevented the effect of epinephrine on plateau duration in a calcium-free solution, extending the plateau duration to more than 3 times normal in some cases. These results are explained in terms of two opposing effects of a change in calcium concentration on plateau formation, one action being through the slow inward current and the second through a shift in a calcium dependence of the inward-rectifying, potassium conductance system.
Insights
Calcium affects guinea pig atrial action potential plateau duration through complex mechanisms. Both calcium concentration and antagonists alter plateau duration and tension, with epinephrine and isoproterenol showing restorative effects.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- The cardiac action potential plateau is crucial for effective heart contraction.
- Calcium ions play a vital role in regulating cardiac electrophysiology and contractility.
Purpose of the Study:
- To investigate the dual effects of calcium concentration on the action potential plateau in guinea pig atria.
- To examine the impact of the calcium antagonist D600 on atrial electrophysiology.
- To explore the modulatory roles of adrenergic agents and calcium chelators on calcium-induced changes.
Main Methods:
- Simultaneous microelectrode and tension recordings in isolated, electrically driven guinea pig atria.
- Manipulation of external calcium concentrations (2.5 mM to lower levels).
- Administration of the calcium antagonist D600 and adrenergic agents (epinephrine, isoproterenol).
Main Results:
- Reducing calcium prolonged the plateau initially, then shortened it; D600 monotonically decreased plateau duration.
- Both protocols reduced steady-state tension, but differentially affected restitution.
- Epinephrine and isoproterenol restored plateau duration; isoproterenol's effect was propranolol-sensitive.
- Calcium chelators enhanced epinephrine's effect on plateau duration in calcium-free solutions.
Conclusions:
- Calcium concentration influences action potential plateau via slow inward current and potassium conductance modulation.
- Adrenergic agents can counteract calcium-depletion effects on atrial electrophysiology.
- Complex interactions between calcium, antagonists, and adrenergic signaling dictate cardiac activation dynamics.