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Am J Physiol Cell Physiol 259: C668-C674, 1990;
0363-6143/90 $5.00
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AJP - Cell Physiology, Vol 259, Issue 4 C668-C674, Copyright © 1990 by American Physiological Society

ARTICLES

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

D. J. Wilkinson and D. C. Dawson
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.

Current fluctuation analysis was used to investigate the properties of 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 microM. 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.microM-1 and k(off) = 744 +/- 53 rad/s, and the microscopic inhibition constant was 67 microM (n = 11). CDPC blocking kinetics were not significantly different after inhibition of Isc by 5 microM serosal carbachol. Single-channel Na+ current (iNa) and the density of open and blocked Na+ channels (N(ob)) were estimated from the fluctuations induced by 40 microM CDPC. Under control conditions, iNa was 0.43 +/- 0.05 pA and N(ob) was 251 +/- 42 X 10(6)/cm2 (n = 10). After exposure to serosal carbachol (2-10 microM) for 60 min, Na+ current and N(ob) were reduced by approximately 50%, but iNa 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.


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H. Hayashi, T. Suzuki, T. Yamamoto, and Y. Suzuki
Cholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colon
Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G617 - G628.
[Abstract] [Full Text] [PDF]


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