G(s) and adenylyl cyclase in transverse tubules of heart: implications forcAMP-dependent signaling

The transverse tubules are highly specialized invaginations of the cardiac sarcolemmal membrane involved in excitation-contraction (EC) coupling. Seve ral proteins directly involved in EC coupling have been shown to reside eit her in the transverse tubular membrane or in closely associated structures. With the use of immunofluorescence microscopy, we have found that G(s) and adenylyl cyclase, key elements in the beta-adrenergic signal transduction cascade, are essentially homogeneously distributed throughout the transvers e tubular network of isolated rat ventricular myocytes. G(s), in particular , was much more abundant within the transverse tubular membrane than in the peripheral sarcolemma. Furthermore, both proteins are also present in the intercalated disk region. The location of these elements of the cAMP-signal ing cascade within a few micrometers of every inotropic target suggests tha t control and action of this second messenger are quite local. Furthermore, a similar distribution is likely for negatively inotropic receptor systems that oppose G(s)-linked receptors at the level of adenylyl cyclase. Thus, in addition to their role in EC coupling, transverse tubules appear to be t he primary site for signaling by inotropic agents.