PHENOTYPIC ALTERATION OF A HUMAN BK (HSLO) CHANNEL BY HSLO-BETA SUBUNIT COEXPRESSION - CHANGES IN BLOCKER SENSITIVITY, ACTIVATION RELAXATION AND INACTIVATION KINETICS, AND PROTEIN-KINASE-A MODULATION/

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