Nicorandil activates glibenclamide-sensitive K+ channels in smooth muscle cells of pig proximal urethra.
نویسندگان
چکیده
The effects of nicorandil on ionic currents recorded from single smooth muscle cells of pig proximal urethra were investigated using patch-clamp techniques. Tension measurement was also performed to study the effects of nicorandil on the resting tone of pig urethra. Nicorandil produced a concentration-dependent sustained outward current that was suppressed by glibenclamide at -50 mV and was carried selectively by K+. In cell-attached configuration, nicorandil activated a 43-pS K+ channel that was reversibly inhibited by 10 microM glibenclamide. This glibenclamide-sensitive 43-pS K+ channel (KGS) "ran down" after excision of the membrane patch. In inside-out configuration, the application of either 1 mM Mg-ATP or 1 mM nucleotide diphosphate reactivated the KGS. In symmetrical 140 mM K+ conditions, 300 microM nicorandil and 300 microM levcromakalim activated a 2.14-pA K+ channel that exhibited the same amplitude and similar channel-opening kinetics. Methylene blue (10-100 microM), a soluble guanylate cyclase inhibitor, did not inhibit the opening of the nicorandil-induced KGS. The KGS was not activated by either sodium nitroprusside (10-100 microM) or 8-bromo guanosine 3':5'-cyclic monophosphate (1 mM). Nicorandil caused a concentration-dependent relaxation of the urethral resting tone but was less potent than levcromakalim. The relaxation induced by 10 microM nicorandil was partially inhibited by glibenclamide (1-10 microM) and also by methylene blue (10-100 microM). These results indicate that two independent nicorandil-induced relaxation mechanisms may be present in pig urethra.
منابع مشابه
Comparative studies on the relaxing action of several adenosine 5'-triphosphate-sensitive K+ channel openers in pig urethra.
The relaxing effects of the adenosine 5'-triphosphate (ATP)-sensitive K+ channel openers (K(ATP) openers; diazoxide, minoxidil, pinacidil, (+/-)-cromakalim, (+)-cromakalim and (-)-cromakalim) were investigated on the resting tone of pig proximal urethra. In addition, patch clamp techniques were utilized for recording cromakalim-induced ionic currents in cells dispersed from the same urethral re...
متن کاملComparative Studies on the Adenosine 5 ' - Triphosphate - Pig Urethra Relaxing Sensitive Action of Several K ' Channel Openers in
The relaxing effects of the adenosine 5'-triphosphate (ATP)-sensitive K' channel openers (KATp openers; diazoxide, minoxidil, pinacidil, (± )-cromakalim, (+)-cromakalim and (-)-cromakalim) were investigated on the resting tone of pig proximal urethra. In addition, patch-clamp techniques were utilized for recording cromakalim-induced ionic currents in cells dispersed from the same urethral regio...
متن کاملSUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil.
1. The classical ATP sensitive K+ (K(ATP)) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K+ channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K+ channel openers, such as pinacidil and nicorandil. 2. In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the effects of these agents on cardiac...
متن کاملجریانهای یونی کانالهای پتاسیمی و کلسیمی در سلولهای ایزوله شده عضله صاف سمینال وزیکول خوکجه و مهاراین جریانها بوسیله Glibenclamide
Smooth muscle cells of seminal vesicle exhibit excitatcry junction patential on nerve stimulation and can fire evoked) action potential (1). However) the type of ion channels that underlie this electrical activity have not been described. I have investigated the type and pharmacology of ion channel in freshly isolated smooth muscle cells from the guinea-pig seminal vesicle using whole-cell patc...
متن کاملEndothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery.
ATP-sensitive K+ channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+ (greater than 10(-4) M). In the inside-out configuration, these channels were activated by extracellular Ca2+ and blocked by cytosolic ATP and gliben...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 280 1 شماره
صفحات -
تاریخ انتشار 1997