Phenotypic Alteration of a Human BK (hSlo) Channel by hSlobeta Subunit Coexpression: Changes in Blocker Sensitivity, Activation/Relaxation and Inactivation Kinetics, and Protein Kinase A Modulation

• Published in: The Journal of neuroscience Vol. 16; no. 15; p. 4543
• Main Authors: Dworetzky, Steven I, Boissard, Christopher G, Lum-Ragan, Janet T, McKay, M. Craig, Post-Munson, Debra J, Trojnacki, Joanne T, Chang, Chia-Ping, Gribkoff, Valentin K
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-08-1996
• Subjects: Alkaloids - pharmacology; Amino Acid Sequence; Base Sequence; Benzylisoquinolines; Calcium - physiology; Calcium Channel Blockers - pharmacology; Cyclic AMP-Dependent Protein Kinases - metabolism; Dose-Response Relationship, Drug; Humans; Molecular Sequence Data; Phenotype; Potassium Channels - physiology
• ISSN: 0270-6474; 1529-2401

A human homolog of the large-conductance calcium-activated potassium (BK) channel beta subunit (hSlobeta) was cloned, and its effects on a human BK channel (hSlo) phenotype are reported. Coexpression of hSlo and hSlobeta, in both oocytes and human embryonic kidney 293 cells, resulted in increased Ca2+ sensitivity, marked slowing of BK channel activation and relaxation, and significant reduction in slow inactivation. In addition, coexpression changed the pharmacology of the BK channel phenotype: hSlo-mediated currents in oocytes were more sensitive to the peptide toxin iberiotoxin than were hSlo + hSlobeta currents, and the potency of blockade by the alkaloid BK blocker tetrandrine was much greater on hSlo + hSlobeta- mediated currents compared with hSlo currents alone. No significant differences in the response to charybdotoxin or the BK channel opener NS1619 were observed. Modulation of BK channel activity by phosphorylation was also affected by the presence of the hSlobeta subunit. Application of cAMP-dependent protein kinase increased P(OPEN) of hSlo channels, but decreased P(OPEN)of most hSlo + hSlobeta channels. Taken together, these altered characteristics may explain some of the wide diversity of BK channel phenotypes observed in native tissues.