CALCIUM-SENSITIVITY OF SMOOTH MUSCLE CONTRACTION IN THE ISOLATED PERFUSED RAT TAIL ARTERY

Abstract

Desensitization and the effects of Bay K 8644 and nifedipine on the calcium-sensitivity of smooth muscle contraction 
were studied in the isolated perfused rat tail artery, employing the activators noradrenaline (NA) (3µM) sand 
potassium chloride (KC1) (100mM). Experiments were conduced in Ca2+ - buffered saline. Activities were added 
when {Ca2+} free was low (1µM) and then {Ca2+ }free was increased stepwise to give a Ca2+ concentration\response 
curve (CRC) There was a progressive rightward shift of the CRCs with time when a series of curves was constructed. 
The higher the calcium concentration to which the tissue was exposed during activation, the greater was 
desensitization. The progressive loss in sensitivity could be attenuated by restricting the range of free calcium used 
for CRCs to between 1µM and 300µM Ca2+. Results were similar whether activation was by NA or high KC1. When 
the tissues were pre-exposed to NA (3µM) (“Priming”) before constructing CRCs, desensitization was produced more 
quickly and thus sensitivity became more “stable”. However, the {Ca2+} during priming and the maximum (Ca2+ ) in a 
CRC determined the stable level, high {Ca2+} reducing sensitivity. Priming and maximum at 300µM ca2+ was optimal 
for avoiding progressive desensitization. Bay K 8644 (0.1µM) decreased the sensitivity to Ca2+ but did not alter the 
rate of desensitization (activated by either NA or KC1). Desensitization complicated demonstration of potentiation by 
Bay K 8644 in the same tissue. Nifedipine (0.1µM) decreased the sensitivity of Ca2+ at the first CRC but thereafter 
CRC’s were not significantly different from their controls. Only a small degree of inhibition could be seen between 
consecutive curves when nifedipine was given after drug-free control responses. Thus the rat tail artery exhibits 
higher sensitivity to Ca2+ on initial contact with activators. The results suggests that desensitization at some stage in 
excitation-contraction coupling, possibly by Ca2+ overload, occurs when high extracellular {Ca2+} (2.5 or 5mM) is 
present during activation by NA. This can be prevented by avoiding high. {Ca2+}, thus allowing prolonged 
reproducibility of high sensitivity to Ca2+ which, is lost.