Possible underestimation of the channel conductance underlying pinacidil-induced K+ currents using noise analysis in pig urethral myocytes.
Electrophysiological and pharmacological properties of the pinacidil-induced K+ currents in isolated cells from pig urethra were investigated using patch-clamp techniques. Pinacidil (100 microM) induced an outward current at -50 mV which gradually decreased. Under current-clamp conditions, 100 microM 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. K(ATP) channel). Analysis of the basal noise of the pinacidil-induced macroscopic currents from -90 mV to -30 mV yielded estimates of channel conductance (6 pS) 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 (K(ATP) channel) in pig urethra.
Teramoto
N
N
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. noritera@linne.med.kyushu-u.ac.jp
Brading
A F
AF
Ito
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D013552:Swine; D014521:Urethra / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D020110:Pinacidil; D005905:Glyburide