KCNQ channels enable reliable presynaptic spiking and synaptic transmission at high-frequency

Abstract

The presynaptic action potential (AP) results in calcium influx which triggers neurotransmitter release. For this reason, the AP waveform is crucial in determining the timing and strength of synaptic transmission. The calyx of Held nerve terminals of rat show minimum changes in AP waveform during high-frequency AP firing. We found that the stability of the calyceal AP waveform requires KCNQ K+ channel activated during high-frequency spiking activity. High-frequency presynaptic spikes gradually led to accumulation of KCNQ channels in open states which kept interspike membrane potential sufficiently negative to maintain Na+ channel availability. Accordingly, blocking KCNQ channels during stimulus trains led to inactivation of presynaptic Na+, and to a lesser extent KV1 channels, thereby reducing the AP height and broadening AP duration. Thus, while KCNQ channels are generally thought to prevent hyperactivity of neurons, we find that in axon terminals these channels function to facilitate high-frequency firing needed for sensory coding. HIGHLIGHTSO_LIKCNQ channels are activated during high-frequency firing C_LIO_LIThe activity of KCNQ channels helps the recovery of Na+ and KV1 channels from inactivation and maintains action potential waveform C_LIO_LIReliable presynaptic action potential waveform preserves stable Ca2+ influx and reliable synaptic signaling C_LI