The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2353-2362
Copyright ©2001 by the American Physiological Society

Peptidergic Modulation of Insect Voltage-Gated Ca²⁺ Currents: Role of Resting Ca²⁺ Current and Protein Kinases A and C

Sächsische Akademie der Wissenschaften zu Leipzig, D-07743 Jena, Germany

Wicher, Dieter Peptidergic Modulation of Insect Voltage-Gated Ca²⁺ Currents: Role of Resting Ca²⁺ Current and Protein Kinases A and C. J. Neurophysiol. 86: 2353-2362, 2001. The modulation of voltage-gated Ca²⁺ currents in isolated dorsal unpaired median (DUM) neurons of cockroach was investigated using whole cell patch clamp. The neuropeptide neurohormone D (NHD), a member of the adipokinetic hormone family, affected Ca²⁺ currents at pico- to nanomolar concentrations. It strongly enhanced currents activating at lower depolarizations, whereas those activating at strong depolarizations were slightly attenuated. The first effect results from upregulation of a previously characterized -conotoxin MVIIC- and -agatoxin IVA-sensitive "mid/low voltage-activated" (M-LVA) Ca²⁺ current. The cAMP-analogue 8-bromo-cAMP, forskolin, and the catalytic subunit of protein kinase A (PKA) mimicked the stimulating action of NHD. In addition, preincubation of neurons with the PKA inhibitor KT 5720 abolished the action of NHD. Thus NHD seems to upregulate the M-LVA current via channel phosphorylation by PKA. Activation of protein kinase C by oleoylacetylglycerol (OAG) mimicked the effect of NHD, and subsequent NHD application only enhanced the current to a moderate extent. On the other hand, inhibition of protein kinase C (PKC) by Gö 6976 abolished the NHD effect. These results indicate that also PKC, too, may play a role in the peptidergic modulation of the M-LVA Ca²⁺ current. The reduction of Ca²⁺ currents in the high-voltage-range is caused by the NHD-induced upregulation of a voltage-independent Ca²⁺ resting current, I_Ca,R, which most probably leads to enhanced Ca²⁺-dependent inactivation of voltage-gated Ca²⁺ currents. To assess the major consequences of the Ca²⁺ current changes, current-clamp investigations were performed. Experiments with iberiotoxin, a specific blocker of BK-type Ca²⁺-dependent K⁺ currents, and the M-LVA current-blocking -toxins suggested that NHD causesvia increasing Ca²⁺-dependent K⁺ currentsa larger hyperpolarization of action potentials. The lowering in the action potential threshold produced by NHD, however, seems to be a direct consequence of the hyperpolarizing shift of the activation curve of total Ca²⁺ current resulting from NHD-induced upregulation of the M-LVA current component.