抄録
Caveolae are involved in various signal transductions across the membrane in cardiac myocytes. Methyl-β-cyclodextrin (MβCD) deprives the cholesterol, an important structural component of caveolae, from plasma membrane. In patch clamp experiments, we found that application of MβCD inhibit the activation of L-type Ca2+ current via β-stimulation in cardiac myocytes. We examined the effects of MβCD application on β-stimulant-induced elevation of cardiac function in Langendorr perfused rat heart. Application of MβCD (1 mM, 30 min) did not affect the basal cardiac function. Following the MβCD treatment (15 min), application of isoproterenol (iso; 10 nM, 15 min) in the presence of MβCD, increased HR from 196.9 ± 17.3 to 336.8 ± 13.0 beats/min, but failed to increase LVDP (75.4 ± 9.1 vs 124.4 ± 12.3%; iso application with and without treatment of MβCD, respectively). MβCD did not affect the inotropic effect of elevated extracellular Ca concentration. These results suggest that treatment of MβCD does not affect L-type Ca2+ channels, but damages the β-stimulation pathway to attenuate activation of L-type Ca2+ currents. It is considered that the relationship of L-type Ca2+ channel, protein kinase A and A kinase-anchoring protein (AKAP) may play important roles in the β-stimulation pathway. MβCD may cause membrane fragility and which is followed by AKAP injury in the membrane and/or damages the linkage between L-type Ca2+ channel and AKAP. [J Physiol Sci. 2007;57 Suppl:S204]
