In the most common forms of signaling, chemical messengers are used to transmit information from one cell to another and, in many cases, guanine nucleotide binding G proteins, coupling receptors to enzyme effectors, play a critical role in the response. Every response seems to include some change in the electrical properties of the cell and of the ionic channels from which these electrical properties are derived. Heretofore such changes were thought to be mediated by cytoplasmic pathways regulated by the G protein effector en zymes, but it is now clear that G proteins also couple membrane receptors to ionic channels by a cytoplasmically independent, membrane-delimited path way. These two pathways have the respective synonyms indirect and direct (Figure 1). Although a membrane intermediary has not yet been excluded, it is likely that ionic channels will join adenylyl cyclase (AC) and cGMP phosphodiesterase (cGMP PDE) and possibly phospholiphase (PLC) and phospholiphase A2 (PLA2) as direct targets for G proteins. Furthermore,