Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na(V)1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by beta adrenergically stimulated G-proteins. We demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.

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