Desensitization of GIRK current in rat atrial myocytes reflects a reduction in K+ driving force

摘要

G protein activated inward-rectifying K+ (GIRK) channels are expressed in the heart, preferentially in the pacemaking and atrial myocytes and in various neurons and endocrine cells. It is well accepted that GIRK channel activation contributes to vagal inhibition of cardiac frequency and shortening of atrial action potentials.Membrane current through atrial and neuronal G protein-gated inwardly-rectifying K+ (GIRK) channels undergoes a fast (acute) desensitization upon rapid activation via appropriate receptors such as the muscarinic M2 receptor in atrial myocytes using a saturating concentration of Acetycholin (ACh) (20pM). Pre-stimulation of GIRK current by a low concentration of ACh or via A1 adenosine receptor results in a reduction of current induced by 20 (mu)M ACh. This reflected a decrease of the desensitization component. It has been proposed that acute desensitization does not represent classic receptor desensitization but reflects either a property of the G protein cycle, or of the channel itself.