Effect of potassium channel blocking agents on the actions of phenylephrine in rabbit taenia caeci.
The effects of tetraethylammonium, apamin, 4-aminopyridine and holding potential on the phenylephrine-evoked outward currents in dispersed smooth muscle cells of the rabbit taenia caeci were analyzed using the whole cell patch clamp method. Phenylephrine (10 mumol/l) under the double sucrose gap condition, substantially hyperpolarized the smooth muscle membrane and reduced the input membrane resistance. This concentration of phenylephrine enhanced the frequency and amplitude of spontaneous transient outward currents (s.t.o.c.s) and elicited a low amplitude sustained outward current which were voltage and temperature dependent. In addition, phenylephrine (10 mumol/l) reduced the outward current evoked by voltage steps. Tetratehylammonium (1-5 mmol/l) attenuated the depolarization-evoked outward current, blocked the appearance of s.t.o.c.s, and fully abolished the phenylehrine induced changes in membrane currents. Apamin (0.1-10 mumol/l) only slightly affected the evoked outward current and s.t.o.c.s. However apamin did not change the phenylephrine-induced outward currents. Pretreatment with 4-aminopyridine (0.5-2 mmol/l) did not reduce the phenylephrine-induced sustained outward current and s.t.o.c.s but prevented the phenylephrine induced reduction of the depolarization-evoked outward current. These results are in favour of assumption that the phenylephrine induced hyperpolarization and reduction in the input membrane resistance are consequences of an enhanced potassium current via tetraethylammonium-sensitive, apamin and 4-aminopyridine resistant potassium channels.
Bauer
V
V
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ito
Y
Y
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002432:Cecum; D005071:Evoked Potentials / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D010656:Phenylephrine; D001030:Apamin; D019789:Tetraethylammonium; D015761:4-Aminopyridine