P. Michelena et al., DRASTIC FACILITATION BY ALPHA-LATROTOXIN OF BOVINE CHROMAFFIN CELL EXOCYTOSIS WITHOUT MEASURABLE ENHANCEMENT OF CA2+ ENTRY OR [CA2+](I), Journal of physiology, 502(3), 1997, pp. 481-496
1. Latrotoxin (LTX, 1-3 nM) caused a gradual increase of the spontaneo
us catecholamine release rate in bovine adrenal chromaffin cells super
fused with normal Krebs-Hepes solution containing 2.5 mM Ca2+. Ca2+ re
moval abolished this effect. LTX enhanced also the secretory responses
to high K+ (35 or 70 mM) and to acetylcholine (ACh, 30 mu M). 2. The
application of Ca2+ pulses to cells previously superfused with a 0 Ca2
+ solution (Krebs-Hepes deprived of CaCl2) induced secretory responses
that gradually reached 400-800 nA of catecholamines, provided that LT
X was present. The responses to ACh or 35 mM K+ pulses (in the presenc
e of Ca2+) were also enhanced by LTX, from around 100-200 nA to over 1
000 nA. Though such enhancement remained in the presence of Ca(2+)chan
nel blockers, it disappeared upon the lowering of [Na+](o) or in elect
roporated cells. 3. Using protocols similar to those of secretion, LTX
did not enhance basal Ca-45(2+) uptake, whole-cell Ca2+ currents or b
asal [Ca2+](1). In fact, LTX attenuated the K+- or ACh-evoked increase
s in C-45(2+) uptake and [Ca2+](i). 4. It is proposed that the secreto
ry response to brief periods of Ca2+ reintroductions is triggered by l
ocal subplasmalemmal Ca-i(2+) transients, produced by the Na+-Ca2+ exc
hanger of the plasma membrane working in the reverse mode. This situat
ion might be physiologically reproduced during ACh stimulation of chro
maffin cells, which is followed by the firing of Na+-dependent action
potentials.