G protein-gated inward rectifier K⁺ (K_G) channels are directly activated the subunits released from pertussis toxin- sensitive G proteins, and contribute to neurotransmitter- induced deceleration of heart beat, formation of slow inhibitory post-synaptic potentials in neurons and inhibition of hormone-release in endocrine cells. The physiological roles of K_G channels are critically determined by mechanisms which regulate their activity and their subcellular localization. K_G channels are tetramers of inward rectifier K⁺ (Kir) channel subunits, Kir3.x. The combination of Kir3.x subunits which go to make up each K_G channel varies among tissues and cell types. Each subunit of the channel possesses one G binding site. The binding of G increases the number of functional K_G channels via a mechanism that can be described by the Monod-Wyman and -Changeux allosteric model. During voltage steps K_G channel current alters time-dependently. The K_G current exhibits inward-rectification due to blockade of outward-going current by intracellular Mg²⁺ and polyamines. Upon repolarization, this blockade is relieved practically instantaneously and then is followed by a slow gating mechanism called 'relaxation'. Relaxation is caused by the voltage-dependent behavior of regulators of G protein signaling (RGS proteins), which accelerate intrinsic GTP hydrolysis by the G subunit. Thus, the relaxation behavior of K_G channels reflects the time-course with which the G protein cycle is altered by RGS protein activity at each membrane potential. Subcellular localization of K_G channels is controlled by several distinct mechanisms, some of which have been recently clarified. The neuronal K_G channel, which contains Kir3.2c, is localized in the postsynaptic density (PSD) of various neurons including dopaminergic neurons in substantia nigra. Its localization at PSD may be controlled by PDZ-domain containing anchoring proteins. The K_G channel in thyrotrophs is localized exclusively on secretary vesicles, which upon stimulation are rapidly inserted into the plasma membrane and causes hyperpolarization of the cell. This mechanism indicates a novel negative feedback regulation of exocytosis. In conclusion, K_G channels are under the control of a variety of signalling molecules which regulate channel activity, subcellular localization and thus their physiological roles in myocytes, neurons and endocrine cells.