Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels.
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% CO(2), extracellular pH (pH(o)) 6.8] induced small, slow spikes. These spikes were inhibited by Co(2+) or nifedipine and were attributed to activation of L-type Ca(2+) channels by HA. Upon inhibition of both Na(+) and Ca(2+) 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% CO(2), 77 mM HCO(3)(-), pH(o) 7.45). Either HA or IH, but not 50 mM Na-propionate, activated Ca(2+) channels. Inhibition of L-type Ca(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(+) channels and TWIK-related acid-sensitive K(+) (TASK) channels. Furthermore, HA and IH activate L-type Ca(2+) channels, and this activation is part of chemosensitive signaling in LC neurons.
Filosa
Jessica A
JA
Department of Physiology and Biophysics, Wright State University School of Medicine, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.
Putnam
Robert W
RW
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D006935:Hypercapnia / Q000503:physiopathology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D015221:Potassium Channels; D013779:Tetrodotoxin