Cardiac 1-Adrenoceptors and Inotropy: Myofilament Ca2+ Sensitivity, Intracellular Ca2+Mobilization, Signaling Pathway, and Pathophysiological Relevance

Cardiac alpha(1)-adrenoceptor stimulation elicits a positive inotropic effect because of myofilament Ca2+ sensitization with a small increase in Ca2+ transients predominantly mediated by alpha(1B)-adrenoceptors via the intracellular alkalinization and potential myosin light chain 2 phosphorylation. However, the alpha(1)-adrenoceptor-mediated inotropy exhibits a wide range of species-dependent variation. In addition, it displays remarkable regional and subtype-dependent variations among species. The signaling pathway for alpha(1)-adrenoceptor-mediated regulation is vulnerable being markedly influenced by experimental and pathophysiological conditions. Cardiac alpha(1)-adrenoceptors may have clinical relevance in that sympathomimetic amines including norepinephrine possess higher affinity to alpha(1)-adrenoceptors than beta-adrenoceptors, and alpha(1)-adrenoceptors play a compensatory role in patients with heart failure. Modulation of cardiac alpha(1)-adrenoceptor-mediated signaling pathway could provide potential targets for the development of novel therapeutic strategy.