Modulation of the dihydropyridine‐sensitive calcium channels in Drosophila by a phospholipase C‐mediated pathway

Abstract

Disruption of phospholipase C‐β (PLC) by the norpA mutations of Drosophila renders flies blind by affecting the light‐evoked photoreceptor potential. We report here that the norpA‐coded PLC modulates the 1,4‐dihydropyridine (DHP)‐sensitive Ca2+ channels in larval muscles. The DHP‐sensitive current was reduced in the norpA mutants. Application of 1 μM phorbol 12‐myristate 13‐acetate (TPA) and 1 μM phorbol 12,13‐didecanoate (PDD), activators of protein kinase C (PKC), rescued the current in the mutant fibers without significantly affecting the normal current. 4α‐phorbol 12,13‐didecanoate (4αPDD), an inactive analog of PDD, did not affect either the normal or the mutant current. One micromolar bisindolylmaleimide (BIM), an inhibitor of PKC, reduced the current in the normal fibers without affecting the mutant current. 300 μM sn‐1,2‐dioctanoyl‐glycerol (DOG), an analog of diacylglycerol (DAG), increased the current in the mutant fibers. These experiments suggest that the DHP‐sensitive Ca2+ channels in Drosophila may be modulated by the PLC‐DAG‐PKC pathway, and that the same PLC isozyme which is involved in phototransduction in the adult flies may also modulate muscle Ca2+ channels in the larval stage of development. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 265–275, 1997

Modulation of L-type Calcium Channels in Drosophila via a Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP)-mediated Pathway

“…Many of these processes are mediated via Components examined in the present study, as well as those studied in two previous reports from this laboratory (16,26), are shown boxed. Underlined text refers to the pharmacological effects studied on these components.…”

“…Females in the amn x8 strain used in our experiments carry an attached X chromosome (34) homozygous for the wild-type amn gene. It has been shown previously that the L-type Ca 2ϩ channel currents recorded from larval muscles are similar between males and females (26). Thus, wild-type female siblings from the amn x8 strain provide a control for the mutant males.…”

“…Control recordings were performed independently for each set of experiments, and percentage effects on currents under different recording conditions were calculated with respect to controls performed specifically for those recording conditions. Recording temperature was maintained at 21°C with a Peltier junction and measured for each larva with a thermocouple probe after the experiment (26).…”

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

“…Despite differences in some pharmacological properties compared with their vertebrate counterparts (49), the Drosophila larval muscle LTCCs are also modulated by PKA (78) and PKC (79). Perturbations of the PKA or PKC pathways that enhance phosphorylation by pharmacological or genetic means increase the Ca 2ϩ current (78,79).…”

Plasticity and Second Messengers During Synapse Development

“…In the eye, PLC and a cPKC are critical to signal transduction (Shieh et al, 2002). At the NMJ, norpA mutants, which disrupt PLC-b function, have a reduction in muscle L-type calcium currents (Gu and Singh, 1997). Application of PKC activators can rescue current levels in the mutant, but have no effect in wild type, suggesting that PKC is a regulator of the basal levels of calcium current in the larval muscle.…”