Guanine nucleotide binding proteins couple a wide variety of receptors to ion channels via both "direct" or membrane-delimited and "indirect" second messenger-mediated pathways. This tutorial summarizes current approaches to defining the mechanisms of guanine nucleotide binding protein-mediated ion channel activation. Two well-characterized ion channels in the heart, namely, the beta-adrenergic receptor-activated calcium channel and the muscarinic receptor-activated potassium channel, are used to illustrate the criteria that can distinguish between direct and indirect guanine nucleotide binding protein-transduced pathways.
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