QUINIDINE BLOCKADE OF THE CARBACHOL-ACTIVATED NONSELECTIVE CATIONIC CURRENT IN GUINEA-PIG GASTRIC MYOCYTES

1 In guinea-gig gastric myocytes isolated from the antral circular lay er, stimulation of muscarinic receptors by carbachol (CCh) induces a c ationic current (I-CCh) which is known as the main mechanism of depola rization induced by muscarinic stimulation. 2 We tested the effects of a number of ion channel blockers on I-CCh and focused upon quinidine which was a highly potent blocker. Externally applied quinidine suppre ssed I-CCh (IC50 = 0.25 mu M) in a reversible and voltage-dependent ma nner. Applied internally, quinidine was about 100 times less potent th an when applied externally. Persistent activation of G-protein by GTP gamma S also induced a cationic current similar to I,,, and this curre nt was also blocked by quinidine. 4-Aminopyridine and tetraethylammoni um also suppressed I-CCh in a dose-dependent manner (IC50 = 3.3 mM and 4.1 mM, respectively). 3 Pretreatment with quinidine (2 mu M) selecti vely 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 sup pressed by quinidine but in a higher concentration range (IC50 = 3 mu M). Quinidine, 10 mu M, decreased the amplitude of the voltage-depende nt Ca current to only a small extent (15% decrease at 0 mV). Quinidine , 2 mu M, 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 abl e to block the CCh-activated cation channel in a non-specific manner a nd among them, quinidine can be used as an effective blocker for I-CCh in guinea-pig gastric myocytes.