Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K super(+) and Ca super(2+) channels

• Published in: American Journal of Physiology: Cell Physiology Vol. 284; no. 1; pp. C145 - C155
• Main Authors: Filosa, JA, Putnam, R W
• Format: Journal Article
• Language: English
• Published: 01.01.2003
• ISSN: 0363-6143
• DOI: 10.1152/ajpcell.00346.2002

We studied chemosensitive signaling in locus coeruleus (LC) neurons using both perforated and whole cell patch techniques. Upon inhibition of fast Na super(+) spikes by tetrodotoxin (TTX), hypercapnic acidosis [HA; 15% CO sub(2), extracellular pH (pH sub(o)) 6.8] induced small, slow spikes. These spikes were inhibited by Co super(2+) or nifedipine and were attributed to activation of L-type Ca super(2+) channels by HA. Upon inhibition of both Na super(+) and Ca super(2+) spikes, HA resulted in a membrane depolarization of 3.52 plus or minus 0.61 mV (n = 17) that was reduced by tetraethylammonium (TEA) (1.49 plus or minus 0.70 mV, n = 7; P < 0.05) and absent (-0.97 plus or minus 0.73 mV, n = 7; P < 0.001) upon exposure to isohydric hypercapnia (IH; 15% CO sub(2), 77 mM HCO sub(3) super(-), pH sub(o) 7.45). Either HA or IH, but not 50 mM Na-propionate, activated Ca super(2+) channels. Inhibition of L-type Ca super(2+) 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 super(+) channels and TWIK-related acid-sensitive K super(+) (TASK) channels. Furthermore, HA and IH activate L-type Ca super(2+) channels, and this activation is part of chemosensitive signaling in LC neurons.