Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

Author:

Teramoto Noriyoshi1,Brading Alison F2,Ito Yushi1

Affiliation:

1. Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

2. University Department of Pharmacology, Mansfield Road, Oxford 0×1 3QT, UK

Abstract

Abstract Electrophysiological and pharmacological properties of the pinacidil-induced K+ currents in isolated cells from pig urethra were investigated using patch-clamp techniques. Pinacidil (100 μM) induced an outward current at −50 mV which gradually decreased. Under current-clamp conditions, 100 μM pinacidil induced a hyperpolarization that was sustained. This suggests that activation of only a few channels can hyperpolarize the membrane. At a holding potential of −50 mV, glibenclamide inhibited the pinacidil-induced current with a single exponential time course. Unitary current recordings in symmetrical 140 mM K+ conditions demonstrated that pinacidil activates a 43-pS, glibenclamide-sensitive K+ channel (i.e. KATP channel). Analysis of the basal noise of the pinacidil-induced macroscopic currents from −90 mV to −30 mV yielded estimates of channel conductance (6pS) which were much smaller, and probably an underestimate. These results indicate that pinacidil induces a glibenclamide-sensitive K+ current through only one type of K+ channel (KATP channel) in pig urethra.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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