ABSTRACT
This study was designed to identify and characterize Na+ -activated K+ current (I(K(Na))) in guinea pig gastric myocytes under whole-cell patch clamp. After whole-cell configuration was established under 110 mM intracellular Na+ concentration ([Na+]i) at holding potential of -60 mV, a large inward current was produced by external 60 mM K+([K+] degree). This inward current was not affected by removal of external Ca2+. K+ channel blockers had little effects on the current (p>0.05). Only TEA (5 mM) inhibited steady-state current to 68+/-2.7% of the control (p<0.05). In the presence of K+ channel blocker cocktail (mixture of Ba2+, glibenclamide, 4-AP, apamin, quinidine and TEA), a large inward current was activated. However, the amplitude of the steadystate current produced under [K+]degree (140 mM) was significantly smaller when Na+ in pipette solution was replaced with K+ - and Li+ in the presence of K+ channel blocker cocktail than under 110 mM [Na+]i. In the presence of K+ channel blocker cocktail under low Cl- pipette solution, this current was still activated and seemed K+ -selective, since reversal potentials (E(rev)) of various concentrations of [K+]degree-induced current in current/voltage (I/V) relationship were nearly identical to expected values. R-56865 (10-20 microgram), a blocker of IK(Na), completely and reversibly inhibited this current. The characteristics of the current coincide with those of IK(Na) of other cells. Our results indicate the presence of IK(Na) in guinea pig gastric myocytes.
Subject(s)
Male , Female , Animals , Tetraethylammonium Compounds/pharmacology , Stomach/physiology , Sodium/metabolism , Potassium Channels/physiology , Potassium Channel Blockers/pharmacology , Myocytes, Smooth Muscle/physiology , Membrane Potentials , Guinea Pigs , Chlorides/pharmacology , Calcium/metabolismABSTRACT
We investigated the effects of piperitenone oxide (PO), a major constituent of the essential oil of Mentha x villosa, on the guinea pig ileum. PO (30 to 740 mug/ml) relaxed basal tonus without significantly alterating the resting membrane potential. In addition, PO relaxed preparations precontracted with either 60 mM K+ or 5 mM tetraethyl-ammonium in a concentration-dependent manner. At concentrations from 0.1 to 10 mug/ml PO potentiated acetylcholine-induced contractions, while higher concentrations (>30 mug/ml) blocked this response. These higher PO concentrations also inhibited contractions induced by 60 mM K+. PO also blocked the components of acetylcholine contraction which are not sensitive to nifedipine or to solutions with nominal zero Ca2+ and EGTA. These results show that PO is a relaxant of intestinal smooth muscle and suggest that this activity may be mediated at least in part by an intracellular effect.
Subject(s)
Guinea Pigs , Animals , Male , Acetylcholine/pharmacology , Anti-Anxiety Agents/pharmacology , Calcium Channel Blockers/pharmacology , Gastrointestinal Agents/pharmacology , Ileum/drug effects , Ketones/pharmacology , Muscle Contraction/physiology , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Nifedipine/pharmacology , Plant Oils/pharmacology , Potassium Chloride/pharmacology , Terpenes/pharmacology , Tetraethylammonium Compounds/pharmacology , Guinea PigsABSTRACT
Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.
Subject(s)
Rabbits , Animals , Aorta/drug effects , In Vitro Techniques , Membrane Potentials/drug effects , Potassium/pharmacology , Potassium Channels/physiology , Tetraethylammonium Compounds/pharmacology , Vanadates/pharmacology , Vasodilation/drug effectsABSTRACT
Esta revisión reúne la información disponible sobre los agentes farmacológicos y toxina sque bloquean los diferentes tipos de corrientes de K+ presinápticas, y discute la importancia relativa de estas corrientes en el control de la liberación fásica y cuántica del transmisor. Los agentes farmacológicos y toxinas que bloquean la corriente rápida de K+ voltaje-dependiente (IKf), aumentan la liberación fásica de actilcolina evocada por el impulso nervioso. Este efecto es debido al aumento del influjo de Ca2+ durante la despolarización de la membrana presináptica. El bloqueo selectivo de la correinte de K+ calcio-dependiente IK(Ca) no produce ningún cambio en la liberación fásica del transmisor, lo cual indica que en condiciones fisiológicas esta corriente no tiene un papel significaivo en la repolarización de la membrana presináptica. La contribución de la corriente lenta de K+ voltaje-dependiente (IKs) en la liberación fásica de acetilcolina no ha sido aún dilucidada. En conclusión, IKf, IK(Ca) e IKs pueden modular la entrada de Ca2ñ en las terminaciones nerviosas motoras; sin embargo, en condiciones fisiológicas solamente IKf tiene una importancia clave, ya que controla el indlujo transitorio de Ca2+ que es responsable d ela liberación fásica del neurotransmisor