Expression and relevance of the G protein-gated K channel in the mouse ventricle.

The atrial G protein-gated inwardly rectifying K (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (MR), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels.

GIRK2 splice variants and neuronal G protein-gated K channels: implications for channel function and behavior.

Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2.

Suppression of inhibitory G protein signaling in forebrain pyramidal neurons triggers plasticity of glutamatergic neurotransmission in the nucleus accumbens core.

Cocaine and other drugs of abuse trigger long-lasting adaptations in excitatory and inhibitory neurotransmission in the mesocorticolimbic system, and this plasticity has been implicated in several key facets of drug addiction. For example, glutamatergic neurotransmission mediated by AMPA receptors (AMPAR) is strengthened in medium spiny neurons (MSNs) in the NAc core and shell during withdrawal following repeated in vivo cocaine administration. Repeated cocaine administration also suppresses inhibitory signaling mediated by G protein-gated inwardly rectifying K (GIRK) channels in pyramidal neurons of the prelimbic cortex, an important source of glutamatergic input to the NAc core that has been implicated in cocaine-seeking and behavioral sensitization.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice.

The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K (GIRK/Kir3) channels mediate the direct inhibitory effect of GABA receptor (GABAR) and D DA receptor (DR) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on DR-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors.