Summary
We have previously shown that pertussis toxin (PTX) stimulates delayed-onset, [Ca2−] a -dependent catecholamine (CA) release from bovine chromaffin cells. We now show that this effect of PTX is inhibited in part (50%) by dihydropyridine Ca2−-channel antagonists niludipine and nifedipine, and is potentiated by the dihydropyridine Ca2+-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−] a , nicotine and muscarine, and here we extend these observations by showing that toxin pretreatment also enhances the secretory response to [Ba2+] a . 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 Ca2+-channel conductance (6 nS/cell at 2.6mm [Ca2+] a ). PTX evoked the activation of a new class of Ca2+-selective channels (5 pS in 25mm [Ca2+]pipet), which are rather insensitive to membrane potential. We have termed theseG-type calcium channels. These data suggest that treatment with PTX not only increases the probability of L-type Ca2+-channel activation at more negative potentials, but also increases the probability of opening of an entirely new, voltage-independent, Ca2+ channel. These actions of PTX should promote Ca2+ entry and might explain the stimulation by the toxin of CA secretion from medullary chromaffin cells in culture.
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Ceña, V., Brocklehurst, K.W., Pollard, H.B. et al. 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. J. Membrain Biol. 122, 23–31 (1991). https://doi.org/10.1007/BF01872736
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DOI: https://doi.org/10.1007/BF01872736