Regulation of the slow Ca++ channels of myocardial cells

Contraction of the heart is regulated by a number of mechanisms, such as neurotransmitters, hormones, autacoids, pH, intracellular ATP, and Ca++ ions. These actions are mediated, at least in part, by actions on the sarcolemmal slow (L-type) Ca++ channels, exerted directly or indirectly. The major mechanisms for the regulation of the slow Ca++ channels of myocardial cells includes the following. cAMP/PK-A phosphorylation stimulates the slow Ca++ channel activity, whereas cGMP/PK-G phosphorylation inhibits. DAG/PK-C phosphorylation and tyrosine kinase phosphorylation are suggested to stimulate the slow Ca++ channel activity. Intracellular application of Gs alpha protein increases the slow Ca++ currents (ICa(L)). Lowering of intracellular ATP inhibits ICa(L). Acidosis and increase in [Ca]i inhibits ICa(L). A number of changes in the Ca++ channels also occur during development and aging. Thus, it appears that the slow Ca++ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors, and thereby control can be exercised over the force of contraction of the heart.