Kv4.2 regulates baseline synaptic strength by inhibiting R-type channel-mediated calcium signaling in the hippocampus

Kv4.2 channels, which mediate A-type K+ current, exert significant influence on synaptic input signals and synaptic plasticity in the principal cells of the hippocampus. While their influence on activity-dependent regulation of synaptic response is well-established, the impact of Kv4.2 channels on baseline synaptic strength remains elusive. To investigate this, we selectively inhibited postsynaptic Kv4.2 by introducing Kv4.2 antibodies into the hippocampal granule cells and evaluated its impact on the baseline synaptic transmission. Our results demonstrated that Kv4.2 inhibitions led to notable increase in the amplitude of AMPA receptor (AMPAR)-mediated synaptic currents, and this effect was in parallel with the Kv4.2 expression level at dendritic regions. This Kv4.2-dependent synaptic potentiation was effectively abolished by intracellular 10 mM BAPTA or block of R-type calcium channels (RTCC) and downstream signaling molecules including protein kinase A (PKA) and protein kinase C (PKC). Importantly, Kv4.2 inhibitions did not occlude further synaptic strengthening high frequency stimulation, suggesting that synaptic strength regulation by Kv4.2 s distinct from the mechanism of long-term potentiation. Our study highlights the role of Kv4.2 in regulating the baseline synaptic strength, where Kv4.2-mediated inhibition of RTCC is crucial.