Significance of the sodium pump for airway smooth muscle

Experiments were carried out to determine if active or passive sensitization and resensitization influence resting membrane potential (Em) and contractile response of airway smooth muscle from tracheal muscle. In active sensitization, Camm-Hartley male guinea pigs were injected with 1 cc of Pertussis vaccine delivered i.p. and 1 cc of 1% albumin administered subcutaneously. Then after a 14 day immunization period, resensitization was carried out with weekly s.c. injections of 0.1% albumin for three consecutive weeks. In passive sensitization normal animals were injected i.p. with serum from repeatedly sensitized animals. Resting membrane potential (Em) of airway smooth muscle cells (ASM) was determined with glass microelectrodes filled with 3 M KCl and having an impedance of between 80-90 M omega. Simultaneously with the measurement of Em, isometric force (IF) was also determined. Both measurements of Em and IF were done before, during and after administration of histamine (10(-3) or 10(-5) M), ouabain (10(-5) M), K+-free solution and 1% ovalbumin. It was found: (I) Active sensitization caused a significant hyperpolarization of airway smooth muscle cells. Em of ASM was equal to -78.1 +/- 0.5 mV (+/- S.E.) after the 3rd resensitization as compared to Em of -61.3 +/- 0.5 mV (+/- S.E.) as seen in controls (P less than 0.001). After passive sensitization Em of ASM increased to -69.5 +/- 0.2 mV (P less than 0.001). (II) Tracheal preparations from resensitized animals showed hyperresponsiveness to histamine (10(-3) M or 10(-5) M). (III) Using ouabain (10(-5) M) and K+-free solution it was shown that the electronic Na+-pump of ASM was potentiated in both actively and passively sensitized animals. Disodium cromoglycate and substance 48/80 failed to influence the level of Em sensitized ASM. It is concluded that the phenomenon of airway hyperreactivity observed following sensitization and resensitization may be directly related to the alteration of airway smooth muscle cell membrane. Sensitization and particularly resensitization caused potentiation of the electrogenic Na+-pump in membrane of airway smooth muscle cells.