The dynamic Na⁺ pump and Kv7 channels contribute to regulation of firing rate through activity-dependent feedback.

(A) Identified vagal motoneurons receiving input from the respiratory rhythm generator exhibit slow afterhyperpolarization following rhythmic burst firing, demonstrating that physiological bursting is followed by prolonged membrane hyperpolarization, consistent with recruitment of the dynamic Na+ pump and Kv7 channels. (B) Current clamp recordings of firing in response to stimulation of current input that mimics synaptic drive in slices. (C) Each neuron showed differential changes in firing rate in response to 2 μM ouabain and 10 μM XE-991 along a spectrum (n = 14 from N = 8 animals). (D) Top example shows a neuron with a large contribution of the Na+ pump for the control of firing rate, with little input from Kv7 channels. Bottom example shows a neuron with little contribution from the pump but a large role for Kv7 in controlling firing rate. (E) Example recordings of resting membrane potential in silent neurons during application of 2 μM ouabain (n = 8 neurons from N = 4 animals), 10 μM XE-991 (n = 8 neurons from N = 4 animals), and 20 μM ouabain to block the “housekeeper” form of the Na+ pump (n = 5 neurons from N = 3 animals). (F) Mean data for effects of each drug on resting membrane potential. The data underlying this figure can be found in S1 Data.