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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 358, Issue 3, pp 374–381 | Cite as

A K+ single channel and whole-cell clamp study on the effects of levcromakalim in guinea pig portal vein cells

  • Christoph A. Karle
  • Xiaozhou Yao
  • V. A. W. Kreye
Original article

Abstract

Single channel cell-attached patch and whole-cell clamp experiments on the mode of action of the K+ channel opener (KCO), levcromakalim, were performed in guinea pig isolated portal vein cells. At +20 mV (135/23 mM K+ in bath/pipette), 10 µM levcromakalim activated K+ channels with a chord conductance of 23.2 pS (KKCO), which were sensitive to the blocker of ATP-dependent K+ channels (KATP), glibenclamide. Voltage steps from –80 mV to +20 mV activated 4-aminopyridine-sensitive K+ channels of 6.5 pS with properties of delayed rectifier K+ channels (Kv). In patches which upon a previous voltage step had revealed the existence of Kv, levcromakalim reduced the open-probability of Kv, but it did not concomitantly activate KKCO. During the course of the experiments, but unrelated to the presence of levcromakalim, large conductance K+ channels (BKCa) appeared which could be inhibited by iberiotoxin, a selective blocker of BKCa, and by the membrane-permeant calcium buffer, BAPTA/AM, but not by glibenclamide. Whole-cell current-voltage (i-V) relations were established in response to voltage ramps from +50 mV to –100 mV; on subtraction of control i-V curves from i-V curves obtained in the presence of 10 µM levcromakalim, the KCO-induced K+ current remained which was proportional to voltage. This is not compatible with the upward-bent curvature predicted by the GHK current equation for purely resistive channels at high [K+]i versus low [K+]o. In conclusion, in the guinea pig portal vein cells, no evidence could be established for the hypotheses that KCOs may act via conversion of Kv to KATP (Beech and Bolton 1989; Edwards et al. 1993) or by activation of BKCa (Balwierczak et al. 1995). In these cells, mild inward rectification of the levcromakalim-induced current was observed which underlines their relationship to KATP in other tissues.

Key words Delayed rectifier Inward rectifier Calcium-activated K+ channel ATP-dependent K+ channel Vasodilator drugs Vascular smooth muscle 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Christoph A. Karle
    • 1
  • Xiaozhou Yao
    • 1
  • V. A. W. Kreye
    • 1
  1. 1.II. Physiologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg, GermanyDE

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