Abstract
Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion.
Highlights
Background channels play a fundamental role in determining the neuronal resting membrane potential, input resistance and excitability [1]
Our goal here is to examine the possible influence of substance P on background K+ channels, which contribute to setting the resting membrane potential and which may modulate the excitability of central pattern generator (CPG) neurons
Our results indicate that substance P inhibits a K+ conductance by interacting with background K+ channels
Summary
Background channels play a fundamental role in determining the neuronal resting membrane potential, input resistance and excitability [1]. The cellular mechanisms underlying the increase in burst frequency include a membrane depolarization and a potentiation of NMDA current [8, 9], as well as a reduction of the crossed. The membrane depolarization is accompanied by an increased input resistance at resting membrane potential suggesting that this effect may be mediated by a decrease in outward background K+ conductance. Our goal here is to examine the possible influence of substance P on background K+ channels, which contribute to setting the resting membrane potential and which may modulate the excitability of central pattern generator (CPG) neurons. 5-HT and substance P have been shown to inhibit background K+ channels of the two-pore, TASK-1 subtype [3] [16] and substance P modulation of the TASK-1 subtype has been implicated in regulating the respiratory rhythm generation [4]. We further present evidence these channels likely belong to the two-pore, TASK-1 K+ channel subtype based on their unique pH sensitivity and the selective blockade by anandamide and AVE1231
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