EFFECTS OF DEPOLARIZING AGENTS ON TRANSGLUTAMINASE ACTIVITY, CA2+ INFLUX, AND PROTEIN-SYNTHESIS IN SUPERIOR CERVICAL AND NODOSE GANGLIA EXCISED FROM RATS

Rapid changes in transglutaminase (TG) activity, Ca-45(2+) - influx and [H-3]leucine incorporation in superior cervical ganglia (SCG), and nodose ganglia (NG) excised from adult rats were examined following addition of membrane-depolarizing agents veratridine (Ver) or high extracellular [K+]o during aerobic incubation in vitro at 37-degrees-C. Addition of KCl (50 mM) stimulated TG activity to a maximal extent (four to six-fold) in SCG and NG after 30 min. Ver (0.2 mM) also increased TG activity in both ganglia after 30 min. Kinetic studies showed that the stimulation of TG activity in both ganglia caused by each depolarization condition was associated with a decrease in K(m) and an increase in V(max) value. The depolarizing agents Ver and high [K+]o also caused significant increases in Ca-45(2+) influx into both ganglia. The Ver-induced increases in TG activity and Ca-45(2) accumulation were antagonized by tetrodotoxin (TTX, 1 muM), a sodium channel blocker. The K+-induced increase in TG activity was not blocked by tetraethylammonium (TEA, 20 mM), a potassium channel antagonist, although TEA did block the K+-induced increase in Ca-45(2+) accumulation. The membrane-perturbing, sialic acid-containing compounds, GM1-ganglioside (GM1, 5 nM) and alpha-sialyl cholesterol (alpha-SC, 20 muM), were moderate inhibitors of the K+-induced effects on TG activity and Ca-45(2+) accumulation. The sialyl compounds had little effect on Ver-induced accumulation of Ca-45(2+) but enhanced the Ver-evoked stimulation in TG activity. These results suggests that the veratridine-and K+-induced increases in TG activity occur via modulation of Ca2+ and Na+ channel gating mechanisms that are pharmacologically distinct for each depolarizing agent. The veratridine- and K+-induced decrease in [H-3]leucine incorporation could be a result of stimulation of TG activity as a consequence of degenerative alterations.