Ca2+ flux and signaling implications by nicotinic acetylcholine receptors in rat medial habenula.
The fraction of inward current carried by Ca(2+) (FCa(2+)) through nicotinic acetylcholine receptors (nAChRs) on acutely isolated rat medial habenula (MHb) neurons was calculated from experiments that simultaneously monitored agonist-induced membrane currents and intracellular [Ca(2+)], measured with patch-clamp and indo-1 fluorescence, respectively. In physiological concentrations of extracellular Ca(2+) (2 mM) at -50 mV, the percentage of current carried by Ca(2+) was determined to be roughly 3-4%, which is in close agreement with measurements from other heteromeric nicotinic receptors expressed in peripheral tissue. Among factors that may have affected this measurement, such as Ca(2+) influx through voltage-gated Ca(2+) channels, the concentration of intracellular Ca(2+) buffer, and Ca(2+) sequestration and release from intracellular stores, only Ca(2+) uptake by mitochondria was shown to confound the analysis. Furthermore, we find that because of the high density of nAChRs on MHb cells, low concentrations of ACh (10 microM) and its hydrolysis product, choline (1 mM), can significantly elevate intracellular Ca(2+). Moreover, during persistent activation of nAChRs, the level of intracellular Ca(2+) is proportional to its extracellular concentration in the physiological range. Together, these findings support the suggestion that nAChRs may be capable of sensing low concentrations of diffusely released neurotransmitter and, in addition, transfer information about ongoing local synaptic activity by changes in extracellular Ca(2+).
Guo
Xiaochuan
X
Department of Neurobiology, McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham AL 35294-2182, USA.
Lester
Robin A J
RA
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000378:metabolism; D005456:Fluorescent Dyes; D019262:Habenula / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D005456:Fluorescent Dyes; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D002118:Calcium