Distinct post-translational modifications regulate BK channel activity The interplay between protein palmitoylation and phosphorylation

摘要

Large conductance, Ca~(2+)-activated K+ channels (BK or maxi-K channels) are expressed in a variety of cell types (i.e. neurons, smooth and skeletal muscle myocytes, endocrine and exocrine cells), and are capable of generating robust hyperpolarizing events in response to membrane depolarizations and/or elevations of cytosolic free Ca2+. In airway and vascular smooth muscles, enhancement of BK channel activity by cAMP- and cGMP-dependent protein kinases, respectively, contributes to the relaxation of these tissues, leading to bronchial dilation and decreased vascular resistance. Anyone who uses the β2-agonist salbutamol (i.e.Ventolin) to reduce asthma or nitroglycerin (cGMP-elevating agent) to treat hypertension and angina pectoris may thus already appreciate that BK channel phosphorylation has important physiologic consequences. In eukaryotes, the BK channel pore-forming α subunit arises from a single gene that can generate multiple splice variants with distinct functional characteristics.