A revised mechanism of action of hyperaldosteronism-linked mutations in cytosolic domains of GIRK4 (KCNJ5).

G protein-gated, inwardly rectifying potassium channels (GIRK) mediate inhibitory transmission in brain and heart, and are present in the adrenal cortex. GIRK4 (KCNJ5) subunits are abundant in the heart and adrenal cortex. Multiple mutations of KCNJ5 cause primary aldosteronism (PA).

A Collision Coupling Model Governs the Activation of Neuronal GIRK1/2 Channels by Muscarinic-2 Receptors.

The G protein-activated Inwardly Rectifying K-channel (GIRK) modulates heart rate and neuronal excitability. Following G-Protein Coupled Receptor (GPCR)-mediated activation of heterotrimeric G proteins (Gαβγ), opening of the channel is obtained by direct binding of Gβγ subunits. Interestingly, GIRKs are solely activated by Gβγ subunits released from Gα-coupled GPCRs, despite the fact that all receptor types, for instance Gα-coupled, are also able to provide Gβγ subunits.

Andersen-Tawil Syndrome Is Associated With Impaired PIP Regulation of the Potassium Channel Kir2.1.

Andersen-Tawil syndrome (ATS) type-1 is associated with loss-of-function mutations in gene. encodes the tetrameric inward-rectifier potassium channel Kir2.1, important to the resting phase of the cardiac action potential.