Glycolytic ATP production regulates muscarinic cation currents in guinea-pig ileum.
We investigated the possible sources of intracellular ATP which was previously shown essential for maintaining the muscarinic cationic channel activities (or currents; I(cat)) in guinea-pig ileal myocytes, using two variants of patch clamp techniques. Deprivation of external glucose or its replacement with 2-deoxyglucose significantly reduced the magnitude of I(cat), recorded with nystatin-perforated method, with greater efficacy than for voltage-dependent Ca2+ current Intracellular dialysis of ileal myocytes with key substrates for glycolysis, oxidative metabolism and creatine-phosphocreatine system all resulted in a comparably effective maintenance of I(cat), which was abolished by inhibitors for these ATP-producing systems, 3-bromopyruvate, cyanide and 2,4-dinitrofluorobenzene (DNFB), respectively. However, amongst these inhibitors, only 3-bromopyruvate effectively reduced I(cat) recorded with the nystatin-perforated method. These results strongly suggest the exclusive physiological importance of glycolytic ATP production in maintaining I(cat), activity, and thus this mechanism may play a role in the regulation of gut motility.
Shi
Juan
J
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Li
Jishuo
J
Ito
Yushi
Y
Inoue
Ryuji
R
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002412:Cations / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006019:Glycolysis / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018408:Patch-Clamp Techniques; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*
D002412:Cations; D003486:Cyanides; D004791:Enzyme Inhibitors; D007473:Ion Channels; D011773:Pyruvates; D011976:Receptors, Muscarinic; D010725:Phosphocreatine; C017092:bromopyruvate; D000255:Adenosine Triphosphate; D004139:Dinitrofluorobenzene; D003401:Creatine