Dominance of P/Q-type calcium channels in depolarization-induced presynaptic FM dye release in cultured hippocampal neurons.
Bottom Line: Analysis of the release kinetics and the fractional release amplitude demonstrate that, whereas in only 15% of the synapses release depended exclusively on P/Q-type channels, the majority of synapses (85%) contained both N- and P/Q-type channels.Nevertheless, the kinetics of FM dye release in synapses containing both channel types was determined by the P/Q-type channels.Together, our data suggest a more direct coupling of P/Q-type channels to synaptic release compared to N-type channels, which may explain the high prevalence of neurological P/Q-type channelopathies.
Affiliation: Division of Physiology, Medical University Innsbruck, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria.Show MeSH
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Mentions: In order to characterize the channel-type composition of individual synapses we generated frequency distribution histograms of Rf values of all individual recorded synapses in the different conditions (Fig. 4) normalized to the mean of the control. The Rf values of the control synapses show a wide normal distribution around the mean of 1.00 ± 0.33 (mean ± SD; Fig. 4A, blue line). In stark contrast, the distribution of the combined CTx and Aga block (Rf 0.29 ± 0.23; mean ± SD; Fig. 4A, orange line) displays a prominent peak at an Rf of approximately 0.2 – representing synapses with maximally blocked release – followed by a smaller population of synapses showing severely reduced release. Cluster analysis revealed that 75% of the synapses fall within this maximally blocked population (Rf 0.18 ± 0.10; mean ± SD; Fig. 4C, light orange area), indicating that release depended on presynaptic N- and P/Q-type channels. The tail of the skewed distribution represents the remaining 25% responding synapses, albeit at a strongly reduced efficacy. Comparing CTx-treated synapses with the control and combined CTx + Aga groups (Fig. 4B) reveals that the distribution of Rf values of CTx blocked synapses (red) is indistinguishable from the control condition (Rf 0.99 ± 0.32; mean ± SD). Thus blocking only N-type channels did neither affect the release properties of the entire synapse population, nor reveal a subpopulation of synapses entirely depended on N-type channels.
Affiliation: Division of Physiology, Medical University Innsbruck, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria.