title: Functional and molecular characterization of maxi K+ -channels (BK(Ca)) in buffalo myometrium.
abstract: Large conductance potassium channels (BK(Ca) channels) play a central role in maintaining myometrial tone, thus activation of these channels proved to have therapeutic potential in preterm labor. Present study aims to unravel the presence of BK(Ca) (maxi-K) channels in buffalo myometrium. Tension experiments, mRNA and protein expression studies were done to characterize BK(Ca) channels in buffalo myometrium. Isolated myometrial preparations exhibited rhythmic spontaneity with regular pattern of amplitude and frequency. Selective blockers of BK(Ca) channels iberiotoxin (IbTx; 100nM) and tetraethylammonium (TEA; 1mM) produced excitatory effects as evidenced by increase in amplitude and frequency of myogenic activity. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimi-dazol-2-one (NS-1619; 10(-7)-10(-4)M), a BK(Ca) channel opener, produced concentration-dependent relaxation of myometrium with pD(2) of 5.02±0.19 and R(max) of 31.35±3.5% (n=5). TEA significantly antagonized NS-1619-induced relaxation (pD(2) of 4.72±0.12 and R(max) of 22.72±1.78%; n=5). IbTx also significantly shifted the dose response curve of NS-1619 towards right (pD(2) of 3.98±0.16; n=4) without significant change in the per cent maximal response. Further, RT-PCR study detected mRNA encoding BK(Ca) α-subunit and Western blot analysis detected its protein expression in myometrium. Based on the results of the present investigation, it is suggested that BK(Ca) channels are present in the buffalo myometrium and are open in the resting state. Thus, their activation by potassium channel opener/β(2)-adrenoceptor agonist (tocolytic drug) may lead to uterine relaxation in preterm labor.
authors: Department of Pharmacology and Toxicology, College of Veterinary Science & Animal Husbandry, Pandit Deen Dayal Upadhyaya Veterinary Sciences University & Cattle Research Institute, Mathura, India.
authors: Soumen
authors: S
authors: Choudhury
authors: Satish Kumar
authors: SK
authors: Garg
authors: Thakur Uttam
authors: TU
authors: Singh
authors: Santosh Kumar
authors: SK
authors: Mishra
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D015153:Blotting, Western / Q000662:veterinary; D002020:Buffaloes / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D009215:Myometrium / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D019789:Tetraethylammonium / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology
chemical_list: D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; C086491:NS 1619; D019789:Tetraethylammonium; C064719:iberiotoxin