T. Yuhi et al., UP-REGULATION OF FUNCTIONAL VOLTAGE-DEPENDENT SODIUM-CHANNELS BY CYCLIC-AMP-DEPENDENT PROTEIN-KINASE IN ADRENAL-MEDULLA, Brain research, 709(1), 1996, pp. 37-43
Treatment of cultured bovine adrenal chromaffin cells with dbcAMP incr
eased [H-3]STX binding with an EC(50) of 126 mu M and a half-effective
time of 12 h; dbcAMP (1 mM x 18 h) raised the B-max approximately 1.5
-fold without altering the K-d value. Forskolin (0.1 mM) or IBMX (0.3
mM) also increased [H-3]STX binding, while dbcCMP had no effect. Effec
ts of dbcAMP and forskolin were abolished by H-89, an inhibitor of cAM
P-dependent protein kinase. Cycloheximide (10 mu g/ml) and actinomycin
D (10 mu g/ml), inhibitors of protein synthesis, nullified the stimul
atory effect of dbcAMP, whereas tunicamycin, an inhibitor of protein g
lycosylation, had no effect. Treatment with dbcAMP augmented veratridi
ne-induced Na-22 influx, Ca-45 influx via voltage-dependent Ca channel
s and catecholamine secretion, while the same treatment did not alter
Ca-45 influx and catecholamine secretion caused by high K (a direct ac
tivation of voltage-dependent Ca channels) [25]. Na influx via single
Na channel calculated from Na-22 influx and [H-3]STX binding was quant
itatively similar between non-treated and dbcAMP-treated cells. Brevet
oxin allosterically enhanced veratridine-induced Na influx approximate
ly 3-fold in dbcAMP-treated cells as in non-treated cells. These resul
ts suggest that cAMP-dependent protein kinase is involved in the modul
ation of Na channel expression in adrenal medulla.