Pertussis toxin stimulation of catecholamine release from adrenal medullary chromaffin cells: mechanism may be by direct activation of L-type and G-type calcium channels.
We have previously shown that pertussis toxin (PTX) stimulates delayed-onset, [Ca2+]o-dependent catecholamine (CA) release from bovine chromaffin cells. We now show that this effect of PTX is inhibited in part (50%) by dihydropyridine Ca(2+)-channel antagonists niludipine and nifedipine, and is potentiated by the dihydropyridine Ca(2+)-channel agonist Bay K-8644. We and others have shown that pretreatment of chromaffin cells with PTX results in enhanced catecholamine secretion in response to high [K+]o, nicotine and muscarine, and here we extend these observations by showing that toxin pretreatment also enhances the secretory response to [Ba2+]o. All these data are consistent with the concept that PTX may act on Ca2+ channels. To examine the possibility of a direct action of the toxin on the voltage-gated L-type Ca2+ channel known to be present in these cells, we studied the effects of the toxin on whole cell Ca2+ currents. We found and report here that spontaneous electrical activity was considerably increased in PTX-treated cells. Our measurements of whole cell inward Ca2+ currents indicate that the underlying mechanism is a marked shift of the activation curve of the L-type Ca2+ current along the voltage axis towards more negative potentials. While treatment of the cells with PTX had no effect on L-type Ca(2+)-channel conductance (6 nS/cell at 2.6 mM [Ca2+]o). PTX evoked the activation of a new class of Ca(2+)-selective channels (5 pS in 25 mM [Ca2+]pipet), which are rather insensitive to membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Ceña
V
V
Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Brocklehurst
K W
KW
Pollard
H B
HB
Rojas
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D037342:Pertussis Toxin; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D004095:Dihydropyridines; D010566:Virulence Factors, Bordetella; D002104:Cadmium; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; C019497:niludipin; D014700:Verapamil; D037342:Pertussis Toxin; D009543:Nifedipine