Ml. Gielow et al., RESOLUTION AND PHARMACOLOGICAL ANALYSIS OF THE VOLTAGE-DEPENDENT CALCIUM CHANNELS OF DROSOPHILA LARVAL MUSCLES, The Journal of neuroscience, 15(9), 1995, pp. 6085-6093
Voltage-dependent calcium channels play a role in many cellular phenom
ena. Very little is known about Ca2+ channels in Drosophila, especiall
y those in muscles. Existing literature on neuronal Ca2+ channels of D
rosophila suggests that their pharmacology may be distinct from that o
f vertebrate Ca2+ channels. This raises questions on the pharmacology
and diversity of Ca2+ channels in Drosophila muscles. Here we show tha
t the Ca2+ channel current in the body-wall muscles of Drosophila larv
ae consists of two main components. One component is sensitive to 1,4-
dihydropyridines and diltiazem, which block vertebrate L-type Ca2+ cha
nnels. The second component is sensitive to amiloride, which blocks ve
rtebrate T-type Ca2+ channels. In contrast to Drosophila brain membran
e preparations in which a majority of the Ca2+ channels are phenylalky
lamine-sensitive but dihydropyridine-insensitive, the major current in
the muscles was dihydropyridine-sensitive but relatively less sensiti
ve to verapamil. This might indicate an underlying tissue specific dis
tribution of distinct subtypes of dihydropyridine/phenylalkylamine-sen
sitive Ca2+ channels in Drosophila. Low verapamil sensitivity of the d
ihydropyridine-sensitive current of Drosophila muscles also set it apa
rt from the vertebrate L-type channels which are sensitive to 1,4-dihy
dropyridines, benzothiazepines as well as phenylalkylamines. The dihyd
ropyridine-sensitive current in Drosophila muscles activated in a simi
lar voltage range as the vertebrate L-type current. As with the verteb
rate current,; blockade by dihydropyridines was voltage dependent. Com
pared to the vertebrate T-type current, the amiloride-sensitive curren
t in Drosophila muscles showed higher activation threshold as well as
slower inactivation. These experiments provide the first clear resolut
ion of a Drosophila Ca2+ current into two distinct components. With th
e previous resolution of the K+ current into four components, Drosophi
la larval muscles now provide one of the few preparations in which the
whole cell current can be resolved completely into individual ionic c
urrents. This will help in determining the role of individual currents
in cellular excitability and other calcium related processes; in anal
yzing structure, function, and regulation of specific types of Ca2+ ch
annels; as well as in understanding the molecular basis of calcium cha
nnel diversity.