{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNG3 encodes the Kv6.3 subunit, an “electrically silent” member of the voltage‐gated potassium (Kv) channel family that does not form functional homotetramers on its own but modulates the biophysical properties of partnering Kv channels when incorporated into heterotetrameric complexes. Early studies demonstrated that Kv6.3 is retained in the endoplasmic reticulum when expressed alone, but it reaches the plasma membrane in heteromeric complexes with Kv2.1, where it alters current kinetics—such as slowing deactivation—and thereby diversifies the functional repertoire of Kv2 channels in excitable cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role as a modulatory subunit in neurons, KCNG3 is expressed in several non‐neuronal tissues. For example, BMP‐2 treatment in human pulmonary artery smooth muscle cells upregulates KCNG3 mRNA along with other Kv subunits, suggesting that Kv6.3 may participate in the regulation of membrane excitability that underlies apoptosis, proliferation, and vascular tone in these cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, de novo expression of Kv6.3 in mesenteric arteries of hypertensive animals has been associated with altered Kv current density and changes in the fractional contribution of Kv2‐mediated currents, pointing to a potential role in the pathogenesis of hypertension."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the urinary bladder, expression of Kv6.3 along with other Kv subunits suggests that heteromultimeric complexes containing Kv6.3 may contribute to setting the resting membrane potential and to the repolarization phase of action potentials in smooth muscle cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, in clinical studies, altered expression of KCNG3 has been linked to disease states; for instance, high levels of KCNG3 expression in gastric cancer tissues have been correlated with poor patient prognosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while significant downregulation of KCNG3 in both aganglionic and ganglionic segments of Hirschsprung disease colons suggests that its expression is associated with normal colonic motility and that its loss may contribute to the pathophysiology of this disorder."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, KCNG3/Kv6.3 functions as an important modulatory subunit that, through its coassembly with functional Kv channel α‐subunits, fine-tunes the electrophysiological properties of various excitable tissues. Its regulated expression—and dysregulation in pathological states—indicates that Kv6.3 plays a multifaceted role in controlling cellular excitability and tissue-specific functions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N Ottschytsch, A Raes, D Van Hoorick, et al. 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