Possible role of disturbed Na+ homeostasis in mouse vas deferens contractile hyperreactivity after imunological sensitization

Abstract

In the present study we have investigated the involvement of sensitized mice immunoglobulins and some electrophysiological alterations that participate to the antigenic sensitization-induced hyperreactivity of isolated mouse vas deferens. Active sensitization was performed by subcutaneous injection of egg albumen. Contractile responses to noradrenaline were isometrically recorded in the isolated vas deferens. Low external Na⁺-induced contractions and rapid cooling contractures were evaluated. Resting membrane potential (Er) and intracellular Na activity were measured in control and actively sensitized vas deferens by using conventional KCl-filled and Na⁺-sensitive microelectrodes respectively. Active sensitization-induced hyperreactivity to noradrenaline was reproduced by in vitro passive sensitization of control vas deferens with sensitized mice immunoglobulins. The inhibition of the nitric oxide synthesis by N-nitro-L-arginine methyl ester (L-NAME) did not change control vas deferens reactivity in vitro to noradrenaline and acetylcholine. Rapid cooling contractures, performed after lowering external Na⁺ concentration, were not altered by active sensitization. However, sensitization increased significantly the strength of the low external Na⁺-induced contractions. In control vas deferens Er was a mean of –49.2±0.3 mV (mean ±SEM). Sensitization resulted in reduction of Er by 14 mV. In sensitized preparations, relative insensitivity of Er to ouabain, external K⁺ removal and cooling were observed. The intracellular Na⁺ activity was increased by about 40% in sensitized vas deferens. It is concluded that sensitization-induced hyperreactivity is mediated by immunoglobulins and produced smooth muscle cells depolarisation. The low Er of sensitized muscle may be partly the result of an increase in membrane permeability to Na⁺ which could interfere with intracellular Ca²⁺ homeostasis.