Verapamil blocks basolateral K+ channels in the larval frog skin.
The short-circuit current (Isc) across isolated skin from larval frogs (Rana catesbeiana) was measured when the tissue was bathed with Na2SO4 Ringer solution on the serosal side and with a Ringer solution containing K+ as the primary cation on the mucosal side. When 150 U/ml nystatin was added to the mucosal solution, the Isc increased from 1.4 +/- 0.1 to 35.4 +/- 4.8 microA/cm2. When verapamil was added to the mucosal and serosal Ringer solutions in concentrations between 2.5 and 80 microM, Isc was inhibited in a stepwise manner. At 80 microM, Isc was reduced by 75.3% to 8.74 +/- 1.14 microA/cm2. Analysis of the inhibition of Isc with the direct linear plot method showed that the blockage of Isc could be described by pseudo-first-order kinetics with a Michaelis constant (Km) of 9.59 +/- 2.20 microM. Fluctuation analysis revealed a Lorentzian component in power spectra obtained from preparations treated with 10-80 microM verapamil. The corner frequency of these Lorentzian components increased in a linear manner over this range of verapamil concentrations. The Km calculated from the ratio of the dissociation and association rate constants (k10/k'01) was 39.5 microM. The single-channel currents (i) calculated from the fluctuation analysis parameters decreased significantly between verapamil concentrations of 10 and 80 microM. It appears that the inhibition of K+ channels in the basolateral membrane of this tissue has at least two components.(ABSTRACT TRUNCATED AT 250 WORDS)
Hillyard
S D
SD
Department of Biological Sciences, University of Nevada, Las Vegas 89154.
Van Driessche
W
W
D000818:Animals; D004594:Electrophysiology; D007814:Larva; D009761:Nystatin / Q000494:pharmacology; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011892:Rana catesbeiana / Q000378:metabolism* / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D014700:Verapamil / Q000494:pharmacology*
D015221:Potassium Channels; D009761:Nystatin; D014700:Verapamil