REGULATION OF THE SLOW CA-CELLS(+ CHANNELS OF MYOCARDIAL)

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 indi rectly. The major mechanisms for the regulation of the slow Ca++ chann els of myocardial cells includes the following, cAMP/PK-A phosphorylat ion stimulates the slow Ca++ channel activity, whereas cGMP/PK-G phosp horylation inhibits. DAG/PK-C phosphorylation and tyrosine kinase phos phorylation are suggested to stimulate the slow Ca++ channel activity. Intracellular application of G(s alpha) protein increases the slow Ca ++ currents (I-Ca(L)). Lowering of intracellular ATP inhibits I-Ca(L). Acidosis and increase in [Ca](i) inhibits I-Ca(L). A number of change s in the Ca++ channels also occur during development and aging. Thus, it appears that the slow Ca++ channel is a complex structure, includin g perhaps several associated regulatory proteins, which can be regulat ed by a number of extrinsic and intrinsic factors, and thereby control can be exercised over the force of contraction of the heart.