Multiple targets of chemosensitive signaling in locus coeruleus neurons: Role of K+ and Ca2+ channels

Jessica A. Filosa, Robert W. Putnam

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Abstract

We studied chemosensitive signaling in locus coeruleus (LC) neurons using both perforated and whole cell patch techniques. Upon inhibition of fast Na+ spikes by tetrodotoxin (TTX), hypercapnic acidosis [HA; 15% CO2, extracellular pH (pHo) 6.8] induced small, slow spikes. These spikes were inhibited by Co2+ or nifedipine and were attributed to activation of L-type Ca2+ channels by HA. Upon inhibition of both Na+ and Ca2+ spikes, HA resulted in a membrane depolarization of 3.52 ± 0.61 mV (n = 17) that was reduced by tetraethylammonium (TEA) (1.49 ± 0.70 mV, n = 7; P < 0.05) and absent (-0.97 ± 0.73 mV, n = 7; P < 0.001) upon exposure to isohydric hypercapnia (IH; 15% CO2, 77 mM HCO3 -, pHo 7.45). Either HA or IH, but not 50 mM Na-propionate, activated Ca2+ channels. Inhibition of L-type Ca2+ channels by nifedipine reduced HA-induced increased firing rate and eliminated IH-induced increased firing rate. We conclude that chemosensitive signals (e.g., HA or IH) have multiple targets in LC neurons, including TEA-sensitive K+ channels and TWIK-related acid-sensitive K+ (TASK) channels. Furthermore, HA and IH activate L-type Ca2+ channels, and this activation is part of chemosensitive signaling in LC neurons.

Original languageEnglish (US)
Pages (from-to)C145-C155
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number1 53-1
Publication statusPublished - Jan 1 2003
Externally publishedYes

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Keywords

  • Acidosis
  • Membrane potential
  • Perforated patch clamp
  • Respiration
  • Whole cell patch clamp

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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