Ca²⁺ dependence and pharmacology of large-conductance K⁺ channels in nonlabor and labor human uterine myocytes

Two populations' Ca²⁺ -dependent (BK(Ca)) and Ca²⁺-independent K⁺ (BK) channels of large conductance were identified in inside-out patches of nonlabor and labor freshly dispersed human pregnant myometrial cells, respectively. Cell-attached recordings from nonlabor myometrial cells frequently displayed BK(Ca) channel openings characterized by a relatively low open-state probability, whereas similar recordings from labor tissue displayed either no channel openings or consistently high levels of channel activity that often exhibited clear, oscillatory activity. In inside-out patch recordings, Ba²⁺ (2-10 mM), 4-aminopyridine (0.1-1 mM), and Shaker B inactivating peptide ('ball peptide') blocked the BK(Ca) channel but were much less effective on BK channels. Application of tetraethylammonium to inside-out membrane patches reduced unitary current amplitude of BK(Ca) and BK channels, with dissociation constants of 46 mM and 53 μM, respectively. Tetraethylammonium applied to outside-out patches decreased the unitary conductance of BK(Ca) and BK channels, with dissociation constants of 423 and 395 μM, respectively. These results demonstrate that the properties of human myometrial large-conductance K⁺ channels in myocytes isolated from laboring patients are significantly different from those isolated from nonlaboring patients.