Loss of caveolin-3-dependent regulation of I_Ca in rat ventricular myocytes in heart failure.

β₂-Adrenoceptors and L-type Ca²⁺ current ( I_Ca) redistribute from the t-tubules to the surface membrane of ventricular myocytes from failing hearts. The present study investigated the role of changes in caveolin-3 and signaling, both of which have previously been implicated in this redistribution. I_Ca was recorded using the whole cell patch-clamp technique from ventricular myocytes isolated from the hearts of rats that had undergone either coronary artery ligation (CAL) or equivalent sham operation 18 wk earlier. I_Ca distribution between the surface and t-tubule membranes was determined using formamide-induced detubulation (DT). In sham myocytes, β₂-adrenoceptor stimulation increased I_Ca in intact but not DT myocytes; however, forskolin (to increase cAMP directly) and H-89 (to inhibit increased and decreased, respectively, I_Ca at both the surface and t-tubule membranes. C3SD peptide (which decreases binding to caveolin-3) inhibited I_Ca in intact but not DT myocytes but had no effect in the presence of H-89. In contrast, in CAL myocytes, β₂-adrenoceptor stimulation increased I_Ca in both intact and DT myocytes, but C3SD had no effect on I_Ca; forskolin and H-89 had similar effects as in sham myocytes. These data show the redistribution of β₂ -adrenoceptor activity and I_Ca in CAL myocytes and suggest constitutive stimulation of I_Ca by duanyu1529 in sham myocytes via concurrent caveolin-3-dependent (at the t-tubules) and caveolin-3-independent mechanisms, with the former being lost in CAL myocytes. NEW & NOTEWORTHY In ventricular myocytes from normal hearts, regulation of the L-type Ca²⁺ current by β₂-adrenoceptors and the constitutive regulation by caveolin-3 is localized to the t-tubules. In heart failure, the regulation of L-type Ca²⁺ current by β₂-adrenoceptors is redistributed to the surface membrane, and the constitutive regulation by caveolin-3 is lost.

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