Cholinergic modulation of apical Na+ channels in turtle colon: Analysis of CDPC-induced fluctuations

D. J. Wilkinson, D. C. Dawson

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Abstract

Current fluctuation analysis was used to investigate the properties apical Na+ channels during muscarinic inhibition of active Na+ absorption. A reversible Na+ channel blocker, 6-chloro-3,5-diaminopyrazine-2-carboxamide (CDPC), was used to induce fluctuations in the short-circuit current (I(sc)). Power density spectra of the CDPC-induced fluctuations exhibited a clearly discernible Lorentzian component, characterized by a corner frequency that was linearly related to CDPC concentration between 20 and 100 μM. The on (k'(on)) and off (k(off)) rate coefficients for the CDPC blocking reaction were k'(on) = 11.1 ± 0.8 rad · s-1 · μM-1 and k(off) = 744 ± 53 rad/s, and the microscopic inhibition constant was 67 μM (n = 11). CDPC blocking kinetics were not significantly different after inhibition of I(sc) by 5 μM serosal carbachol. Single-channel Na+ current (i(Na)) and the density of open and blocked Na+ channels (N(ob)) were estimated from the fluctuations induced by 40 μM CDPC. Under control conditions, i(Na) was 0.43 ± 0.05 pA and N(ob) was 251 ± 42 x 106/cm2 (n = 10). After exposure to serosal carbachol (2-10 μM) for 60 min, Na+ current and N(ob) were reduced by ~ 50%, but i(Na) was not changed significantly. These results indicate that muscarinic inhibition of electrogenic Na+ absorption was associated with a reduction in the number of open Na+ channels in the apical membrane. They also suggest that this downregulation of transport involved a coordinated decrease in both apical and basolateral membrane conductances.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume259
Issue number4 28-4
Publication statusPublished - 1990
Externally publishedYes

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Keywords

  • acetylcholine
  • amiloride
  • carbachol
  • noise analysis

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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