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

Westudied chemosensitive signaling in locus coeruleus (LC) neurons usingboth perforated and whole cell patch techniques. Upon inhibition offast Na⁺ spikes by tetrodotoxin (TTX), hypercapnic acidosisHA; 15% CO₂, extracellular pH (pH_o) 6.8]induced small, slow spikes. These spikes were inhibited byCo²⁺ or nifedipine and were attributed to activation ofL-type Ca²⁺ channels by HA. Upon inhibition of bothNa⁺ and Ca²⁺ spikes, HA resulted in a membranedepolarization of 3.52 ± 0.61 mV (n = 17) thatwas 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 HCO, pH_o 7.45).Either HA or IH, but not 50 mM Na-propionate, activatedCa²⁺ channels. Inhibition of L-type Ca²⁺channels by nifedipine reduced HA-induced increased firing rate andeliminated IH-induced increased firing rate. We conclude that chemosensitive signals (e.g., HA or IH) have multiple targets in LCneurons, including TEA-sensitive K⁺ channels andTWIK-related acid-sensitive K⁺ (TASK) channels.Furthermore, HA and IH activate L-type Ca²⁺ channels, andthis activation is part of chemosensitive signaling in LC neurons.