Ion channels in respiratory rhythm generation and sensorimotor integration.

Breathing movements depend on rhythmic neural activity in brainstem nuclei whose constituent neurons are well characterized. Knowing the sites and cells underlying the behavior enables us to identify the roles of individual ion channels. They accomplish three tasks: regulate excitability via the balance of intrinsic currents that govern baseline membrane potential and tonic firing; generate bursts to drive the motor output pattern; and transduce blood-gas levels, lung volume, and air qualities. Here, we explain how sodium and mixed cation channels (sodium leak channel non-selective [NALCN], NaV1.6, and transient receptor potential [TRP] melastatin 4 [TRPM4]) both regulate excitability and generate bursts and how potassium (predominantly two-pore domain acid-sensitive potassium [TASK]-2) and mixed cation (PIEZO and TRP) channels encode sensory feedback to central control circuits. These mechanisms underlie normal breathing and sigh breaths. Breathing is a mammalian behavior in which rhythmogenesis and sensorimotor integration can be understood at multiple levels of analysis from microcircuits and cells to ion channels and genes.