Key result
Apamin application boosted excitatory postsynaptic potentials to 148.2% of baseline in CaV2.3 null mice, demonstrating that Ca2+ influx through CaV2.3 channels is not necessary to activate synaptic SK2-containing channels.
The study supports a model where SK2-containing channels are functionally coupled to NMDARs, and KV4.2-containing channels to CaV2.3 channels, providing negative feedback regulation of EPSPs in CA1 pyramidal neurons.
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Questions CaV2.3 necessity for SK2-mediated EPSP regulation in mice; leaves open translational relevance to human synaptic physiology.
SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R-type Ca2+ channels. Recent studies have challenged the functional coupling between NMDARs and SK2-containing channels, suggesting that synaptic SK2-containing channels are instead activated by Ca2+ entry through R-type Ca2+ channels. Furthermore, SNX has been implicated to have off target affects, which would challenge the proposed coupling between R-type Ca2+ channels and KV4.2-containing K+ channels. To reconcile these conflicting results, we evaluated the effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3 null mice. The results show that in the absence of CaV2.3 channels, apamin application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers on EPSPs observed in neurons from wild type mice was not observed in neurons from CaV2.3 null mice. These data are consistent with a model in which SK2-containing channels are functionally coupled to NMDARs and KV4.2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons.
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Wang et al. (2015) studied this question. Apamin vs. Baseline aCSF / Wild type mice was evaluated on Evoked excitatory postsynaptic potentials (EPSPs) amplitude (p=<0.001). Apamin application boosted excitatory postsynaptic potentials to 148.2% of baseline in CaV2.3 null mice, demonstrating that Ca2+ influx through CaV2.3 channels is not necessary to activate synaptic SK2-containing channels.
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