Effects of calmodulin inhibitors on the cellular metabolism of 45Ca and 210Pb

Altered Ca++ homeostasis may result from the direct inhibition of calmodulin-dependent or -independent transport processes. Changes in cell function not directly related to the transport of Ca, e.g., uncoupling of oxidative phosphorylation or altered membrane permeability also disrupt cell calcium metabolism. Thus, the effects of the calmodulin inhibitor W-13 on cell Pb++ metabolism may be due to its direct effects on Pb++ transporting Ca++ pumps, or indirectly as a result of changes in Ca++ homeostasis. Direct comparison of the effects of W-13 on the metabolism of Pb and Ca is impaired by differences in the kinetic distribution and behavior of Pb and Ca. A further complication is that the calmodulin-dependent processes are most active during periods of elevated intracellular Ca++. The preliminary experiments reported here were conducted in unstimulated cells which have a low resting level of cytosolic Ca++. Therefore, W-13 induced alterations in cell Ca++ and Pb++ may not reflect the changes which could occur in stimulated cells. 1 ref., 1 fig