Denervation-induced supersensitivity to calcium of chemically skinned smooth muscle of the guinea-pig vas deferens

Chronic denervation of the smooth muscle of the guinea-pig vas deferens results in postjunctional supersensitivity. A partial membrane depolarization contributes to the enhanced sensitivity. However, there is evidence that supersensitivity results in part from cellular alterations other than membrane potential changes. In the present study we investigated the possibility that changes in the sensitivity of the contractile proteins may contribute to the phenomenon. The approach was to evaluate the concentration-response relationship for calcium of 'skinned' preparations of guinea-pig vas deferens. The tissues were chemically skinned with either triton X-100 or saponin. Concentration-response curves for calcium were constructed 1 week after postganglionic denervation of one of a pair of vas deferentia. The curve for denervated tissues was shifted significantly to the left of control (1.5-fold at the level of the EC₅₀). In addition to supersensitivity, denervated skinned preparations exhibited a faster rate of contraction. The phenothiazine compounds trifluperazine, fluphenazine and chlorpromazine relaxed skinned muscles which were contracted with calcium. The relaxation was concentration-dependent, and was less pronounced in denervated vasa deferentia than in controls. These results suggest that increased sensitivity of the contractile proteins may contribute to the denervation-induced supersensitivity of smooth muscle, and further that this may be related to a change in the activity or amount of calmodulin