Key result
Phenylephrine increases L-type Ca2+ current by ~49%, prolonging action potential duration in neonatal myocardium.
Why the study?
The mechanisms underlying α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were not fully defined.
Demonstrates that α-adrenoceptor-mediated positive inotropy in neonatal mice relies on L-type Ca2+ channel influx and action potential prolongation.
No immediate implications for neonatal therapy; hypothesis-generating for α-adrenoceptor inotropy in immature myocardium.
Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SEA0400, a selective Na+/Ca2+ exchanger inhibitor. Phenylephrine increased the L-type Ca2+ channel current and prolonged the action potential duration, while the voltage-dependent K+ channel current was not influenced. In the presence of cromakalim, an ATP-sensitive K+ channel opener, the phenylephrine-induced prolongation of action potential duration, as well as the positive inotropy, were smaller than in the absence of cromakalim. These results suggest that the α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca2+ influx through the L-type Ca2+ channel, and the concomitant increase in action potential duration acts as an enhancing factor.
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Hamaguchi et al. (2023) studied Neonatal mouse ventricular myocardium. Phenylephrine vs. Absence of phenylephrine was evaluated on L-type Ca2+ channel current (peak inward current at 0 mV). Phenylephrine increased L-type Ca2+ channel current and prolonged action potential duration, mediating positive inotropy in neonatal mouse ventricular myocardium.
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