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 Ca2+-dependent K+ current. This current produces a post-spike hyperpolarization (AHPslow) that plays a critical role in the regulation of membrane excitability and is responsible for spike-frequency accommodation in these neurons. Inhibition of the AHPslow 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 AHPslow 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 AHPslow are due, in part, to Ca2+ discharge from an intracellular Ca2+-induced Ca2+ release (CICR) pool. Action potential-evoked Ca2+ influx via either L or N type Ca2+ channels triggers CICR. Surprisingly, although L type channels generate 60% of action potential-induced CICR, only Ca2+ influx through N type Ca2+ channels can trigger the CICR-dependent AHPslow. These observations suggest that a close physical proximity exists between endoplasmic reticulum ryanodine receptors and plasma membrane N type Ca2+ channels and AHPslow potassium channels. Such an anatomical relation might be particularly beneficial for modulation of spike-frequency adaptation in vagal afferent neurons.
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD 21201-1559, USA.
R
R
Cordoba-Rodriguez
K A
KA
Moore
J P
JP
Kao
D
D
Weinreich
D000200:Action Potentials; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D005071:Evoked Potentials; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology*; D015230:Prostaglandin D2 / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017997:Leukotriene C4; D012701:Serotonin; D006632:Histamine; D015232:Dinoprostone; D015230:Prostaglandin D2; D001920:Bradykinin; D002118:Calcium