Unique Excitation-contraction Characteristics of Mouse Myocardium As Revealed by SEA0400, a Specific Inhibitor of Na+-Ca2+ Exchanger

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2005 Jul 9

PMID 16003546

Citations 14

Authors

Hikaru Tanaka

Iyuki Namekata

Kentaro Takeda

Akihiro Kazama

Yoshiko Shimizu

Rina Moriwaki

Wataru Hirayama

Akira Sato

Toru Kawanishi

Koki Shigenobu

Affiliations

Soon will be listed here.

Abstract

The functional role of the sodium-calcium exchanger in mouse ventricular myocardium was evaluated with a newly developed specific inhibitor, SEA0400. Contractile force and action potential configuration were measured in isolated ventricular tissue preparations, and cell shortening and Ca2+ transients were measured in indo-1-loaded isolated ventricular cardiomyocytes. SEA0400 increased the contractile force, cell shortening and Ca2+ transient amplitude, and shortened the late plateau phase of the action potential. alpha-adrenergic stimulation by phenylephrine produced a sustained decrease in contractile force, cell shortening and Ca2+ transient amplitude, which were all inhibited by SEA0400. Increasing the contraction frequency resulted in a decrease in contractile force in the absence of drugs (negative staircase phenomenon). This frequency-dependent decrease was attenuated by SEA0400 and enhanced by phenylephrine. Phenylephrine increased the Ca2+ sensitivity of contractile proteins in isolated ventricular cardiomyocytes, while SEA0400 had no effect. These results provide the first pharmacological evidence in the mouse ventricular myocardium that inward current generated by Ca2+ extrusion through the sodium-calcium exchanger during the Ca2+ transient contributes to the action potential late plateau, that alpha-adrenoceptor-mediated negative inotropy is produced by enhanced Ca2+ extrusion through the sodium-calcium exchanger, and that the negative staircase phenomenon can be explained by increased Ca2+ extrusion through the sodium-calcium exchanger at higher contraction frequencies.

Citing Articles

Developmental Changes in the Excitation-Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals.

Hamaguchi S, Agata N, Seki M, Namekata I, Tanaka H J Cardiovasc Dev Dis. 2024; 11(9).

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Regulation of APD and Force by the Na/Ca Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue.

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