cAMPとカルシウムによる心機能制御

抄録

Catecholamine signal is a major mechanism of regulating cardiac function. Norepinephrine released from the synaptic terminal binds to beta adrenergic receptors, leading to the activation of the stimulatory G protein and thus adenylyl cyclase. Cyclic AMP generated by adenylyl cyclase activates protein kinase A, which initiates multiple phosphorylation reactions within cardiac myocytes. A major impact of catecholamine stimulation is the enhancement of Ca cycling within myocytes. In the past decade, multiple molecules have been identified that are involved in Ca cycling. Transgenic studies using mouse models have elucidated the function of such molecules. Indeed, a growing body of evidence has shown that Ca cycling and Ca-dependent signaling pathways play a pivotal role in cardiac hypertrophy and heart failure. In addition, recent studies identified that mutations of the genes encoding sarcoplasmic reticulum proteins cause human cardiomyopathies and lethal ventricular arrhythmias. The regulation of Ca homeostasis via the SR proteins may have potential therapeutic value for heart diseases such as cardiomyopathy, heart failure and arrhythmias. Similarly, molecular mechanisms of catecholamine signal have been elucidated and the diversity of cAMP signal within the heart has been demonstrated. For example, it is now well known that the heart expresses multiple isoforms of adenylyl cyclase. The role of each adenylyl cyclase isoform is different in regulating cardiac function and the viability of cardiac myocytes under normal and pathological conditions. We will summarize our recent progresses in the study of this pathway in the heart. [J Physiol Sci. 2006;56 Suppl:S26]