New Aspects for the Treatment of Cardiac Diseases Based on the Diversity of Functional Controls on Cardiac Muscles: Diversity in the Excitation–Contraction Mechanisms of the Heart

Journal of Pharmacological Sciences

Hikaru Tanaka¹  Iyuki Namekata¹  Hideaki Nouchi¹  Toru Kawanishi²  Akira Takahara¹  Koki Shigenobu¹ 

[1] Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan;Division of Drugs, National Institute of Health Science, Japan

关键词: heart;    action potential;    contraction;    calcium ion;    autonomic nervous system;    cardiac disease;   

DOI  :  10.1254/jphs.08R22FM

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(13)The waveform of the myocardial action potential (AP) triggering contraction differs among the species, developmental stage, and pathological state. The species difference in heart rate, which inversely correlates with body size, originates in the ion-channel mechanisms responsible for diastolic depolarization of the sinoatrial node. In some cases, such as the chronically AV-blocked dog and 11- to 13-day chick embryo, the repolarization reserve is decreased making the heart useful for drug evaluation. The degree of dependence of contraction on sarcoplasmic reticulum (SR) function increases during development. The large SR dependence and short AP of the adult mouse and rat support their rapid contraction under high heart rate. The function of the Na+/Ca2+ exchanger is affected by AP waveform and ion concentrations; its major role is Ca2+ extrusion, but under pathological conditions such as ischemia-reperfusion, it allows Ca2+ influx and leads to myocardial injury, including loss of mitochondrial function. The role of mitochondria in ATP supply is less in the fetus where glycolysis plays a greater role. The pharmacological properties of the myocardium are affected by all of these factors and also by autonomic innervation and the hormonal status. Such comprehensive understanding is indispensable for the development of novel therapeutic strategies.

【 授权许可】

Unknown