Role of Voltage-Gated K⁺ Channels and K2P Channels in Intrinsic Electrophysiological Properties and Saltatory Conduction at Nodes of Ranvier of Rat Lumbar Spinal Ventral Nerves

Abstract

Ion channels at the nodes of Ranvier (NRs) are believed to play essential roles in intrinsic electrophysiological properties and saltatory conduction of action potentials (AP) at the NRs of myelinated nerves. While we have recently shown that two-pore domain potassium (K2P) channels play a key role at the NRs of Ab-afferent nerves, K 1 channels and their functions at the NRs of mammalian motor nerves remain elusive. Here we addressed this issue by using ex vivo preparations of lumbar spinal ventral nerves from both male and female rats and the pressure-patch-clamp recordings at their NRs. We found that depolarizing voltages evoked large noninactivating outward currents at NRs. The outward currents could be partially inhibited by voltage-gated K 1 channel blockers, largely inhibited by K2P blockers and cooling temperatures. Inhibition of the outward currents by voltage-gated K 1 channel blockers, K2P blockers, or cooling temperatures significantly altered electrophysiological properties measured at the NRs, including resting membrane potential, input resistance, AP width, AP amplitude, AP threshold, and AP rheobase. Furthermore, K2P blockers and cooling temperatures significantly reduced saltatory conduction velocity and success rates of APs in response to high-frequency stimulation. Voltage-gated K 1 channel blockers reduced AP success rates at high-frequency stimulation without significantly affecting saltatory conduction velocity. Collectively, both K2P and voltage-gated K 1 channels play significant roles in intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. The effects of cooling temperatures on saltatory conduction are at least partially mediated by K2P channels at the NRs.

Function of KCNQ2 channels at nodes of Ranvier of lumbar spinal ventral nerves of rats

“…The increase of input resistance at NRs may account for the significant decrease of AP rheobase by linopirdine in the present study. The effects of linopirdine on the intrinsic electrophysiological properties at NRs of lumbar spinal ventral nerves are generally consistent with our recent study using classical voltage-gated K + blockers including TEA and 4-AP plus Cs + [ 28 ]. In contrast to linopirdine, we show that retigabine reduces input resistance and increase AP rheobase, a results further support the role of KCNQ2 in regulating intrinsic properties at NRs of lumbar spinal ventral nerves.…”

“…Linopirdine shows no significant effect on AP conduction velocity in the present study. Consistently, voltage-gated K + channel blockers TEA and 4-AP plus Cs + also had no significant effect on AP conduction velocity in our recent study [ 28 ]. Interestingly, while linopirdine increases AP success rates at high frequency stimulation in the present study, voltage-gated K + channel blockers TEA and 4-AP plus Cs + produced an opposite effect in our recent study [ 28 ].…”

“…KCNQ2 channels significantly contribute to functional voltage-gated K + channels at NRs of lumbar spinal ventral nerves. The presence of voltage-gated K + channels at NRs of lumbar spinal ventral nerves have recently been demonstrated by voltage-gated K + channel blockers TEA and 4AP plus Cs + which partially inhibit non-inactivating outward currents at the NRs [ 28 ]. A previous immunohistochemical study shows that Kv3.1b channels are also expressed at NRs of CNS nerves [ 9 ].…”

“…However, it is currently unknown whether voltage-gated K + channels other than KCNQ2 may be expressed at NRs of PNS nerves [ 9 , 10 , 25 ]. It should be noted that most part of non-inactivating outward currents at NRs are mediated by K2P channels in myelinated nerves of PNS [ 5 , 15 , 28 ]. In the present study, retigabine only slightly potentiated non-inactivating outward currents at NRs, which may be partially due to the overwhelming K2P channels at NRs of these nerves.…”

“…Voltage-gated K + channels appear to be functionally insignificant in trigeminal Aβ-afferent nerves of rats as reported in our previous study [ 15 ]. However, in lumbar spinal ventral nerves, we have recently shown that voltage-gated K + channel blockers TEA and 4-AP plus Cs + alter both passive and active membrane properties at NRs, suggesting a significant role of voltage-gated K + channels in regulating intrinsic electrophysiological properties [ 28 ]. It is currently unknown whether KCNQ2 channels are functional voltage-gated K + channels at NRs of lumbar spinal ventral nerves and if so, what specific roles KCNQ2 channels may play in intrinsic electrophysiological properties and saltatory conduction at NRs of the motor nerves.…”