The influence of changes in extracellular and intracellular sodium concentration on detrusor contractility.
OBJECTIVE
To determine the role of Na+-Ca2+ exchange in the regulation of isolated detrusor smooth muscle contractility.


METHODS
Isolated guinea-pig detrusor strips were used to record isometric tension generated by; (a) electrical-field stimulation to elicit nerve-mediated responses; and (b) adding carbachol or superfusing with a high-K+ solution. The [Na+] gradient between extracellular and intracellular compartments was altered by: (i) reducing superfusate [Na+] in stages from 140.2 to 10.2 mm; (ii) addition of the cardiac glycoside strophanthidin (200 microm). RESULTS Reducing extracellular [Na+] reversibly reduced the magnitude of nerve-mediated contractions but increased the resting tension and magnitude of carbachol-induced contracture. The mean (sd) [Na+] required for a half-maximum effect on attenuating contractions, at 85.9 (6.2) mm, and developing contracture, at 59.1 (14.3) mm, were significantly different. The time constants of changes to nerve-mediated contractions and carbachol contracture were also significantly different, at 147 (5) vs 1207 (386) s, respectively. These differences suggest that separate mechanisms influence nerve-mediated contraction and contracture in low-Na+ solutions. Exposure to the cardiac glycoside strophanthidin produced a similar effect to low-Na+ solutions for carbachol contracture. Low-Na+ solutions had no significant effect on contractures induced by high extracellular [K+]. CONCLUSION Reducing the transmembrane [Na+] difference increases intracellular [Ca2+]. This increase is largely accommodated in intracellular stores, that can be released by exogenous carbachol. The results are consistent with the presence of a functional Na+-Ca2+ exchanger in the surface membrane. The lack of effect of low-Na+ solutions on contractures evoked by membrane depolarization is consistent with this conclusion. The reduction of the nerve-mediated contraction by low-Na+ solution might result from blockade of the nerve action potential.
Besarani
Dler
D
Institute of Urology, University College London, London, UK.
Wu
Changhao
C
Fry
Christopher H
CH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D045604:Extracellular Fluid / Q000378:metabolism; D006168:Guinea Pigs; D007424:Intracellular Fluid / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*
D019831:Sodium-Calcium Exchanger; D002217:Carbachol; D012964:Sodium; D002118:Calcium