Direct regulation of cardiac Ca2+ channels by G proteins: neither proven nor necessary?

The cardiac L-type Ca2+ channel has served as a model for ion channel regulation for over a decade. The Ca2+ current is increased by beta-adrenoceptor stimulation and this effect is inhibited by muscarinic acetylcholine receptor stimulation. It is well established that beta-adrenoceptor stimulation increases this current largely by cAMP-dependent phosphorylation but recently data have been presented that suggest that this channel may also be regulated directly by G proteins. This review by Criss Hartzell and Rodolphe Fischmeister evaluates evidence for this second regulatory pathway and concludes that, although G proteins affect cardiac Ca2+ channels in bilayers and excised patches, there is little evidence that this pathway is physiologically significant.