Quinidine blockade of the carbachol‐activated nonselective cationic current in guinea‐pig gastric myocytes

This is the authors' abstract. We don't add key points for this paper.

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.

No immediate clinical implications from this animal model; leaves open quinidine's utility in gastric ion channel research.