PT  - JOURNAL ARTICLE
AU  - Qian, Jing
AU  - Noebels, Jeffrey L.
TI  - Presynaptic Ca<sup>2+</sup> Influx at a Mouse Central Synapse with Ca<sup>2+</sup> Channel Subunit Mutations
AID  - 10.1523/JNEUROSCI.20-01-00163.2000
DP  - 2000 Jan 01
TA  - The Journal of Neuroscience
PG  - 163--170
VI  - 20
IP  - 1
4099  - http://www.jneurosci.org/content/20/1/163.short
4100  - http://www.jneurosci.org/content/20/1/163.full
SO  - J. Neurosci.2000 Jan 01; 20
AB  - 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, α1A subunit) andlethargic (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 ω-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 β4appears 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.