Presynaptic Ca2+ influx at a mouse central synapse with Ca2+ channel subunit mutations

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Abstract

Genetic alterations in Ca2+ channel subunits can be used to study the interaction among channel subunits and their roles in channel function. P/Q- and N-type Ca2+ channels reside at the presynaptic terminal and control the release of neurotransmitter at mammalian central synapses. We used fluorescence imaging techniques to investigate presynaptic Ca2+ currents and neurotransmitter release at hippocampal Schaffer collateral synapses in both tottering (tg, α(1A) subunit) and lethargic (lh, β4 subunit) mutant mice. Application of selective toxins revealed a large reduction in presynaptic P/Q-type Ca2+ transients, from 39% of total in +/+ mice to 6% in tg/tg mice, whereas the proportion of N-type increased from 35 to 68%, respectively. Neurotransmitter release in the tg/tg mutant relied almost exclusively on N-type channels, as shown by the complete blockade of synaptic transmission with α-conotoxin GVIA. Remarkably, loss of β4, a subunit predicted to regulate the subcellular targeting and modulation of both P/Q- and N-type channels, resulted in no significant difference in the ratio of Ca2+ channel subtypes or Ca2+ dependence of neurotransmitter release in lethargic mice. G-protein-mediated inhibition of Ca2+ channels was also unaltered. These results indicate that a profound decrease in presynaptic P/Q-type currents leads to dependence of neurotransmitter release on N-type channels. In contrast, absence of β4 appears not to compromise either P/Q- or N-type channel function at this hippocampal synapse, implicating rescue of presynaptic Ca2+ currents by other available β subunits. The present study reveals compensatory molecular mechanisms in the regulation of presynaptic Ca2+ entry and neurotransmitter release.

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APA

Qian, J., & Noebels, J. L. (2000). Presynaptic Ca2+ influx at a mouse central synapse with Ca2+ channel subunit mutations. Journal of Neuroscience, 20(1), 163–170. https://doi.org/10.1523/jneurosci.20-01-00163.2000

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