G protein independent regulation of ion channels

Many G protein coupled receptors, including ß2 adrenergic receptors, exhibit G protein independent signal transduction (Chapter 7). This mechanism of effector activation/inhibition adds a further dimension to the mechanisms by which GPCRs regulate ion channel function. Thus, for example, the metabotropic glutamate receptor mGluR1 (Chapter 29) generates an excitatory postsynpatic current in hippocampal CA3 pyramidal neurones that arises because of a G protein independent activation of a src-family tyrosine kinase associated signalling pathway that, in turn, activates a non-specific cationic conductance (Heuss et al. 1999).

It is believed that src associates with mGluR1 either directly or via an adaptor protein similar to the situation in P2 adrenergic receptors where stimulated receptors form a complex with activated c-src bound to P-arrestin (a deactivator of G protein mediated signalling; Chapter 7). One possibility is that Homer proteins fulfil this function, another is that an SH3 domain on mGluR1 directly interacts with the tyrosine kinase. Other direct interactions of mGluRs with ion channels, such as the ligand gated ionotropic NMDA receptor, have also been suggested (Chapter 7).

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