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

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 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.

Modulation of the excitability of cholinergic basal forebrain neurones by KATP channels

“…These values are similar to that which have been reported in several other central neurones (Ohno‐Shosaku & Yamamoto, 1992; Schwanstecher & Panten, 1993) and consistent with the reported unitary conductance values for channels composed of SUR1–K ir 6.2 (pancreatic β cell type) subunits (50–75 pS; Findlay et al 1985; Ashcroft et al 1988; Williams et al 1993). By contrast SUR2A–K ir 6.2 (cardiac ventricular type) containing channels have conductances of 67–90 pS (Nakayama et al 1991; Babenko et al 1998 b ; Kono et al 2000) whilst SUR2B–K ir 6.2 (smooth muscle type) channels range between 27 and 59 pS (Koh et al 1998; Lee et al 1999; Teramoto et al 2000).…”

Measuring and evaluating the role of ATP-sensitive K+ channels in cardiac muscle

“…Examples where non-stationary noise analysis has been used to estimate channel conductance and channel number exist for the smooth muscle K ATP channel [37–39] as well as heterologously expressed K ATP channels [40–41]. A direct comparison of this technique with unitary current analysis indicated that the unitary conductance (and therefore channel number) may be seriously underestimated using this technique [42]. …”