Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K and Ca channels

Filosa, Jessica A., and Robert W. Putnam. Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K and Ca2 channels. Am J Physiol Cell Physiol 284: C145–C155, 2003. First published September 18, 2002; 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 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 TWIKrelated 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.