Quinidine blockade of the carbachol-activated nonselective cationic current in guinea-pig gastric myocytes.
1. In guinea-pig gastric myocytes isolated from the antral circular layer, stimulation of muscarinic receptors by carbachol (CCh) induces a cationic current (ICCh) which is known as the main mechanism of depolarization induced by muscarinic stimulation. 2. We tested the effects of a number of ion channel blockers on ICCh and focused upon quinidine which was a highly potent blocker. Externally applied quinidine suppressed ICCh (IC50 = 0.25 microM) in a reversible and voltage-dependent manner. Applied internally, quinidine was about 100 times less potent than when applied externally. Persistent activation of G-protein by GTP gamma S also induced a cationic current similar to ICCh and this current was also blocked by quinidine. 4-Aminopyridine and tetraethylammonium also suppressed ICCh in a dose-dependent manner (IC50 = 3.3 mM and 4.1 mM, respectively). 3. Pretreatment with quinidine (2 microM) selectively blocked the acetylcholine (ACh)-induced depolarization which was recorded in the multicellular tissues by a conventional intracellular microelectrode technique. 4. Voltage-dependent K-currents were also suppressed by quinidine but in a higher concentration range (IC50 = 3 microM). Quinidine, 10 microM, decreased the amplitude of the voltage-dependent Ca current to only a small extent (15% decrease at 0 mV). Quinidine, 2 microM, also suppressed only a minute proportion of the Ca-activated K current (11.1% decrease at 45 mV). 5. From these experiments, it is concluded that some organic agents known as K channel blockers are able to block the CCh-activated cation channel in a non-specific manner and among them, quinidine can be used as an effective blocker for ICCh in guinea-pig gastric myocytes.
Kim
S J
SJ
Department of Physiology & Biophysics, Seoul National University College of Medicine, Korea.
Ahn
S C
SC
So
I
I
Kim
K W
KW
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000037:antagonists & inhibitors; D002412:Cations / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects; D013270:Stomach / Q000166:cytology / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D002412:Cations; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019789:Tetraethylammonium; D002217:Carbachol; D015761:4-Aminopyridine; D019204:GTP-Binding Proteins; D011802:Quinidine; D000109:Acetylcholine