Excitatory effect of ATP on acutely dissociated ventromedial hypothalamic neurons of the rat.
The ATP-induced increase in the cytosolic Ca(2+) concentration ([Ca]i) and current in acutely dissociated ventromedial hypothalamic rats neurons were investigated using fura-2 microfluorometry and the nystatin-perforated patch recording method, respectively. The ATP-induced [Ca]i increase was mimicked by dimethyl-thio-ATP and ATPgammaS, and was inhibited by P2 purinoreceptor antagonists. The ATP-induced [Ca]i increase was markedly reduced by removal of external Na(+) or Ca(2+), and by addition of various Ca(2+) channel antagonists. ATP induced a transient inward current exhibiting a strong inward rectification at membrane potentials more positive than -20 mV. The ATP-induced current at a holding potential of -70 mV was concentration-dependent with a half-maximum effective concentration of 26 microM. Increasing the external Ca(2+) concentration to 10 mM shifted the dose-response relationship to the right. ATP induced only a small current and a small increase in [Ca]i, even at 10 mM Ca(2+), when external Na(+) was removed, suggesting the relatively low permeability to Ca(2+) of purinoceptor channels. These results suggest that ATP activates non-selective cation channels by acting on P2X purinoceptors on dissociated ventromedial hypothalamic neurons, which in turn increases [Ca]i by increasing Ca(2+) influx through voltage-dependent Ca(2+) channels.
Sorimachi
M
M
Department of Physiology, Faculty of Medicine, Kagoshima University, Japan. ciliary@m.kufm.kagoshima-u.ac.jp
Ishibashi
H
H
Moritoyo
T
T
Akaike
N
N
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
D015220:Calcium Channels; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D015222:Sodium Channels; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium; D015032:Zinc; D002118:Calcium