Ethanol-Induced Suppression of G Protein-Gated Inwardly Rectifying K-Dependent Signaling in the Basal Amygdala.

Background: The basolateral amygdala (BLA) regulates mood and associative learning and has been linked to the development and persistence of alcohol use disorder. The GABAR (gamma-aminobutyric acid B receptor) is a promising therapeutic target for alcohol use disorder, and previous work suggests that exposure to ethanol and other drugs can alter neuronal GABAR-dependent signaling. The effect of ethanol on GABAR-dependent signaling in the BLA is unknown.

Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying K Channels.

G protein-gated inwardly rectifying K (GIRK) channels are critical mediators of excitability in the heart and brain. Enhanced GIRK-channel activity has been implicated in the pathogenesis of supraventricular arrhythmias, including atrial fibrillation. The lack of selective pharmacological tools has impeded efforts to investigate the therapeutic potential of cardiac GIRK-channel interventions in arrhythmias.

Bidirectional Influence of Limbic GIRK Channel Activation on Innate Avoidance Behavior.

Systemic administration of ML297, a selective activator of G-protein-gated inwardly rectifying K (GIRK) channels, decreases innate avoidance behavior in male C57BL/6J mice. The cellular mechanisms mediating the ML297-induced suppression of avoidance behavior are unknown. Here, we show that systemic ML297 administration suppresses elevated plus maze (EPM)-induced neuronal activation in the ventral hippocampus (vHPC) and basolateral amygdala (BLA) and that ML297 activates GIRK1-containing GIRK channels in these limbic structures.

Impact of Acute and Persistent Excitation of Prelimbic Pyramidal Neurons on Motor Activity and Trace Fear Learning.

Drug-induced neuroadaptations in the mPFC have been implicated in addictive behaviors. Repeated cocaine exposure has been shown to increase pyramidal neuron excitability in the prelimbic (PL) region of the mouse mPFC, an adaptation attributable to a suppression of G protein-gated inwardly rectifying K (GIRK) channel activity. After establishing that this neuroadaptation is not seen in adjacent GABA neurons, we used viral GIRK channel ablation and complementary chemogenetic approaches to selectively enhance PL pyramidal neuron excitability in adult mice, to evaluate the impact of this form of plasticity on PL-dependent behaviors.

VU0810464, a non-urea G protein-gated inwardly rectifying K (K 3/GIRK) channel activator, exhibits enhanced selectivity for neuronal K 3 channels and reduces stress-induced hyperthermia in mice.

Background And Purpose: G protein-gated inwardly rectifying K (K 3) channels moderate the activity of excitable cells and have been implicated in neurological disorders and cardiac arrhythmias. Most neuronal K 3 channels consist of K 3.1 and K 3.

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.