Mg. Lopez et al., VERATRIDINE-INDUCED OSCILLATIONS OF CYTOSOLIC CALCIUM AND MEMBRANE-POTENTIAL IN BOVINE CHROMAFFIN CELLS, Journal of physiology, 482(1), 1995, pp. 15-27
1. Veratridine (VTD) induced large oscillations of the cytosolic Ca2concentration ([Ca2+](i)) and the membrane potential (V-m) in otherwis
e silent bovine chromaffin cells loaded with fura-a. 2. Depletion of t
he intracellular Ca2+ stores by thapsigargin or ryanodine did not affe
ct these oscillations. Caffeine had a complex effect, decreasing them
in cells with high activity but increasing them in cells with low acti
vity. 3. The [Ca2+](i) oscillations required extracellular Ca2+ and Na
+ and were blocked by Ni2+ or tetrodotoxin. They were antagonized by h
igh external concentrations of Mg2+ and/or Ca2+. 4. The oscillations o
f V-m had three phases: (i) slow depolarization (20 mV in 10-40 s); (i
i) further fast depolarization (30 mV in 1 s); and (iii) rapid (5 s) r
epolarization. [Ca2+](i) decreased during (i), increased quickly durin
g (ii) with a 1 s delay with regard to the peak depolarization; and de
creased during (iii). 5. Slight depolarizations increased the frequenc
y of the oscillations whereas large depolarizations decreased it. 6. T
he Ca2+-dependent K+ channel blocker apamin increased the duration and
decreased the frequency of the oscillations. 7. We propose the follow
ing mechanism for the oscillations: (i) the membrane depolarizes slowl
y by a decrease of potassium conductance (g(K)), perhaps due to a grad
ual decrease of [Ca2+](i); (ii) the threshold for activation of Na+ ch
annels (decreased by VTD) is reached, producing further depolarization
and recruiting Ca2+ channels, and inactivation of both Ca2+ and VTD-p
oisoned Na+ channels is slow; and (iii) g(K) increases, aided by activ
ation of Ca2+-dependent K+ channels by the increased [Ca2+](i), and th
e membrane repolarizes. The contribution of the Na+ channels seems ess
ential for the generation of the oscillations. 8. Bovine chromaffin ce
lls have the machinery required for [Ca2+](i) oscillations even though
the more physiological stimulus tested here (high K+, field electrica
l stimulation, nicotinic or muscarinic agonists) produced mainly non-o
scillatory responses.