Ca(2+) changes induced by different presynaptic nicotinic receptors in separate populations of individual striatal nerve terminals.
Presynaptic nicotinic acetylcholine receptors likely play a modulatory role in the nerve terminal. Using laser-scanning confocal microscopy, we have characterized physiological responses obtained on activation of presynaptic nicotinic receptors by measuring calcium changes in individual nerve terminals (synaptosomes) isolated from the rat corpus striatum. Nicotine (500 nM) induced Ca(2+) changes in a subset (10-25%) of synaptosomes. The Ca(2+) responses were dependent on extracellular Ca(2+) and desensitized very slowly (several minutes) on prolonged exposure to agonist. The nicotine-induced Ca(2+) responses were dose-dependent and were completely blocked by dihydro-beta-erythroidine (5 microM), differentially affected by mecamylamine (10 microM) and alpha-conotoxin MII (100 nM), and not affected by alpha-bungarotoxin (500 nM). Immunocytochemical studies using well-characterized monoclonal antibodies revealed the presence of the alpha4 and alpha3/alpha5 nicotinic subunits. The nicotine-induced responses were unaffected by prior depolarization or by a mixture of Ca(2+) channel toxins including omega-conotoxin MVIIC (500 nM), omega-conotoxin GVIA (500 nM) and agatoxin TK (200 nM). Our results indicate that nicotinic receptors present on striatal nerve terminals induce Ca(2+) entry largely without involving voltage-gated Ca(2+) channels, most likely by direct permeation via the receptor channel itself. In addition, at least two subpopulations of presynaptic nicotinic receptors reside on separate terminals in the striatum, suggesting distinct modulatory roles.
Department of Pharmacology and Physiology, Medical College of Pennsylvania/Hahnemann University, Philadelphia 19102, USA.
S V
SV
Nayak
J J
JJ
Dougherty
J M
JM
McIntosh
R A
RA
Nichols
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000502:physiology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D004079:Dihydro-beta-Erythroidine; D011189:Potassium Chloride; D009538:Nicotine; D002118:Calcium