Ca2+ dependence and pharmacology of large-conductance K+ channels in nonlabor and labor human uterine myocytes.
Two populations, Ca(2+)-dependent (BKCa) and Ca(2+)-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 BKCa 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 BKCa channel but were much less effective on BK channels. Application of tetraethylammonium to inside-out membrane patches reduced unitary current amplitude of BKCa and BK channels, with dissociation constants of 46 mM and 53 microM, respectively. Tetraethylammonium applied to outside-out patches decreased the unitary conductance of BKCa and BK channels, with dissociation constants of 423 and 395 microM, 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.
Khan
R N
RN
Department of Pharmacology, University of Cambridge, United Kingdom.
Smith
S K
SK
Morrison
J J
JJ
Ashford
M L
ML
D015761:4-Aminopyridine / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007743:Labor, Obstetric / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011247:Pregnancy; D012016:Reference Values; D019789:Tetraethylammonium / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D001464:Barium; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D002118:Calcium