Up-regulation of functional voltage-dependent sodium channels by cyclic AMP-dependent protein kinase in adrenal medulla.
Treatment of cultured bovine adrenal chromaffin cells with dbcAMP increased [3H]STX binding with an EC50 of 126 microM and a half-effective time of 12 h; dbcAMP (1 mM x 18 h) raised the Bmax approximately 1.5-fold without altering the Kd value. Forskolin (0.1 mM) or IBMX (0.3 mM) also increased [3H]STX binding, while dbcGMP had no effect. Effects of dbcAMP and forskolin were abolished by H-89, an inhibitor of cAMP-dependent protein kinase. Cycloheximide (10 microgram/ml) and actinomycin D (10 microgram/ml), inhibitors of protein synthesis, nullified the stimulatory effect of dbcAMP, whereas tunicamycin, an inhibitor of protein glycosylation, had no effect. Treatment with dbcAMP augmented veratridine-induced 22Na influx, 45Ca influx via voltage-dependent Ca channels and catecholamine secretion, while the same treatment did not alter 45Ca influx and catecholamine secretion caused by high K (a direct activation of voltage-dependent Ca channels) [25]. Na influx via single Na channel calculated from 22Na influx and [3H]STX binding was quantitatively similar between non-treated and dbcAMP-treated cells. Brevetoxin allosterically enhanced veratridine-induced 22Na influx approximately 3-fold in dbcAMP-treated cells as in non-treated cells. These results suggest that cAMP-dependent protein kinase is involved in the modulation of Na channel expression in adrenal medulla.
Yuhi
T
T
Department of Pharmacology, Miyazaki Medical College, Japan.
Wada
A
A
Kobayashi
H
H
Yamamoto
R
R
Yanagita
T
T
Niina
H
H
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004594:Electrophysiology; D009498:Neurotoxins / Q000494:pharmacology; D012530:Saxitoxin / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013268:Stimulation, Chemical; D015854:Up-Regulation
D009498:Neurotoxins; D015222:Sodium Channels; D012530:Saxitoxin; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases