Calcium regulation of a slow post-spike hyperpolarization in vagal afferent neurons

Activation of distinct classes of potassium channels can dramatically affect the frequency and the pattern of neuronal firing. In a subpopulation of vagal afferent neurons (nodose ganglion neurons), the pattern of impulse activity is effectively modulated by a Ca(2+)-dependent K(+) current. This current produces a post-spike hyperpolarization (AHP(slow)) that plays a critical role in the regulation of membrane excitability and is responsible for spike-frequency accommodation in these neurons. Inhibition of the AHP(slow) by a number of endogenous autacoids (e.g., histamine, serotonin, prostanoids, and bradykinin) results in an increase in the firing frequency of vagal afferent neurons from <0.1 to >10 Hz. After a single action potential, the AHP(slow) in nodose neurons displays a slow rise time to peak (0.3–0.5 s) and a long duration (3–15 s). The slow kinetics of the AHP(slow) are due, in part, to Ca(2+) discharge from an intracellular Ca(2+)-induced Ca(2+) release (CICR) pool. Action potential-evoked Ca(2+) influx via either L or N type Ca(2+) channels triggers CICR. Surprisingly, although L type channels generate 60% of action potential-induced CICR, only Ca(2+) influx through N type Ca(2+) channels can trigger the CICR-dependent AHP(slow). These observations suggest that a close physical proximity exists between endoplasmic reticulum ryanodine receptors and plasma membrane N type Ca(2+) channels and AHP(slow) potassium channels. Such an anatomical relation might be particularly beneficial for modulation of spike-frequency adaptation in vagal afferent neurons.