Affiliation:
1. Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
Abstract
SUMMARY
Voltage-gated calcium channels in the Cav2 channel class are regulators of synaptic transmission and are highly modified by transmitter inputs that activate synaptic G-protein-coupled receptors (GPCRs). A ubiquitous form of G-protein modulation involves an inhibition of mammalian Cav2.1 and Cav2.2 channels by Gβγ dimers that can be relieved by high-frequency trains of action potentials. Here, we address whether the ubiquitous and versatile form of G-protein regulation in mammals is also found in simpler invertebrate nervous systems. Remarkably, the invertebrate LCav2 channel from the pond snail, Lymnaea stagnalis, does not bear any of the hallmarks of mammalian, voltage-dependent G-protein inhibition of Cav2.2. Swapping either the I-II linker or N-terminus of Cav2.2, which serve as key binding domains for G-protein inhibition, does not endow invertebrate LCav2 channels with voltage-dependent G-protein modulatory capacity. Instead, in vitro expressed LCav2 channels are inhibited slowly by the activation of cAMP, in a manner that depends on G-proteins but does not depend on Gβγ subunits. A similar G-protein and cAMP-dependent inhibition of nifedipine-insensitive LCav2 currents is also consistent in native and identified Lymnaea VD4 neurons. The slower inhibition using a cellular messenger such as cAMP may meet the modulatory needs in invertebrates while an activity-dependent regulation, evolving in vertebrates, provides a more dynamic, fine-tuning of neurosecretion by regulating the influence of neurotransmitter inputs through presynaptic GPCRs.
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
Cited by
19 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献