Differential distribution of ionic channels and muscarinic receptors at the cat tracheal neuromuscular junction.
The ionic and pharmacological properties of atropine-sensitive excitatory junction potentials (EJPs) were investigated by the double sucrose gap and microelectrode membrane potential recording methods, and compared with those of inward currents evoked by carbachol (I(CCh)), in cat tracheal smooth muscle. A single and repetitive field stimulation (10-30 V, 50 micros, 20 Hz) evoked atropine-inhibitable EJPs and associated twitch-like contractions. Reduction in external Na+ concentration strongly, but in the external Cl- concentration, decreased the EJP amplitude after 5 min superfusion, although prolonged exposure to low Cl- solutions attenuated the EJPs modestly. Chloride channel blockers such as 9-AC and niflumic acid (each 100 microM), at concentrations high enough to inhibit I(CCh) almost completely, failed to abolish the EJPs. Pirenzepine, AF-DX116 and 4-DAMP all effectively inhibited the EJPs at their concentrations to block respective muscarinic receptor subtypes relatively specifically, while depletion of internal stores by 10 mM caffeine and/or 3 microM ryanodine caused only a partial decrease in the EJP amplitude. These properties are considerably different from those of I(CCh) which is activated exclusively through activation of the M3 receptor/IP3-mediated Ca2+ release pathway and reflects mostly a Ca2+-dependent Cl- current, and suggests the differential distribution of muscarinic receptors and ionic channels inside and outside of the cholinergic neuromuscular junction of this muscle.
Tanaka
K
K
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Inoue
R
R
Ikarashi
Y
Y
Maruyama
Y
Y
Sugimachi
K
K
Ito
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002415:Cats; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D005260:Female; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D000697:Central Nervous System Stimulants; D018118:Chloride Channels; D007473:Ion Channels; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D012433:Ryanodine; D002110:Caffeine; D000109:Acetylcholine