Various roles of voltage-gated calcium channels (VGCCs) in spontaneous glutamate release

Synaptic homeostasis balances neuronal activity at the synapse, preventing neural networks from reaching extremes.

If left unchecked natural mechanisms of neuronal plasticity could turn into runaway excitation or complete degradation of a connection. Importantly, mechanisms for synaptic homeostasis may be linked to epileptogenesis. Although mechanisms for synaptic homeostatic regulation are illusive and not yet completely understood; new research from University College London Institute of Neurology certainly adds evidence to the discussion.

One possible mechanism for synaptic homeostasis involves action potential-independent, spontaneous, miniature neurotransmitter release as it is thought to be involved with maintenance of spines in glutamateric synapses. To gain further understanding of Ca²⁺ regulation of miniature release Ermolyuk et al. looked at the various roles of voltage-gated calcium channels (VGCCs) in spontaneous glutamate release.

The research, published in Nature Neuroscience in December 2013, suggested that VGCC-dependent minis could be directly triggered by the formation of fast transient Ca²⁺ nano/microdomains around individual spontaneously opening channels. This finding is contradictory of the present interpretation that several voltage-gated Ca²⁺ Channels are needed to trigger spontaneous glutamate release.

To understand their findings the group constructed a quantitative model of presynaptic Ca²⁺ dynamics and activation of vesicular fusion in spontaneous and evoked glutamate release. They found that stochastic opening of a single VGCC can trigger vesicular fusion, with a heavy dependence on both VGCC-distance and open-channel duration. In particular R-type VGCCs were ~30 fold more efficient at triggering vesicular fusion than P/Q – and N-type channels; consistent with R-types longer duration of spontaneous channel opening.

Paper details:

Ermolyuk, Y., Alder, F., Surges, R., Pavlov, I., Timofeeva, Y., Kullmann, D. and Volynski, K. Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca²⁺ channels. Nature Neuroscience: 16: (12):1754–1763 (2013) doi: 10.1038/nn.3563