科研之友
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摘要
A novel potassium ion current induced by muscarinic stimulation (IKACh2) is characterized in atrial cardiomyocytes of teleost fishes (crucian carp, Carassius carassius; rainbow trout, Oncorhynchus mykiss) by means of the whole- cell patch- clamp technique. The current is elicited in atrial, but not ventricular, cells by application of carbamylcholine (CCh) in moderate to high concentrations (10(- 7)- 10(-4) mol l(-1)). It can be distinguished from the classic I-KACh, activated by the - subunit of the Gi- protein, because of its low sensitivity to Ba2+ ions and distinct current- voltage relationship with a very small inward current component. Ni2+ ions (5 mmol l- 1) and KBR7943 (10- 5 mol l- 1), non- selective blockers of the sodium- calcium exchange current (INCX), strongly reduced and completely abolished, respectively, the IKACh2. Therefore, IKACh2 was initially regarded as a CCh- induced outward component of the INCX. However, the current is not affected by either exclusion of intracellular Na+ or extracellular Ca2+, but is completely abolished by intracellular perfusion with K+free solution. Atropine (10- 6 mol l- 1), a non- selective muscarinic blocker, completely eliminated the IKACh2. A selective antagonist of M2 cholinoreceptors, AF- DX 116 (2x10- 7 mol l- 1) and an M3 antagonist, 4- DAMP (10- 9 mol l- 1), decreased IKACh2 by 84.4% and 16.6%, respectively. Pertussis toxin, which irreversibly inhibits Gi- protein coupled to M2 receptors, reduced the current by 95%, when applied into the pipette solution. It is concluded that IKACh2, induced by stimulation of M2 cholinoceptors and subsequent Gi- protein activation, represents a new molecular target for the cardiac parasympathetic innervation.
- 出版日期2014-5
