A new potassium ion current induced by stimulation of M2-cholinoreceptors in fish atrial myocytes

Abstract

A novel potassium ion current induced by muscarinic stimulation (IKACh2) is characterized in atrial cardiomyocytes of teleost fishes (crucian carp, Carassius carassius L.; rainbow trout, Oncorhynchus mykiss W.) 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 and high concentrations (10-7 - 10-4 M). It can be distinguished from the classic IKACh, activated by βγ-subunit of the Gi-protein, due to its low sensitivity to Ba2+ ions and distinct current-voltage relationship with a very small inward current component. Ni2+ ions (5 mM) and KB-R7943 (10-5 M), 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 M), a non-selective muscarinic blocker, completely eliminated the IKACh2. A selective antagonist of M2 cholinoreceptors, AF-DX 116 (2×10-7M) and a M3 antagonist, 4-DAMP (10-9M), 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.

Electrical excitability of the heart in a Chondrostei fish, the Siberian sturgeon (Acipenser baerii)

“…IKACh was induced by 10 M carbacholine (CCh) in the external saline. IKACh was obtained as a difference current in the presence of CCh and CCh ϩ 1 M atropine, a specific blocker M2 receptors (1,51).…”

Transcript expression of inward rectifier potassium channels of Kir2 subfamily in Arctic marine and freshwater fish species

“…In atrial and ventricular myocytes, I K1 is the main ion current that determines the negative resting membrane potential, and therefore the strength of depolarization needed to bring membrane potential to the firing threshold of the cardiac AP. In atrial myocytes, the acetylcholine-sensitive inward rectifier current (I KAch ) may also contribute to the resting membrane potential (Abramochkin et al 2014;Molina et al 2007). At the threshold potential, the density of the depolarizing I Na exceeds the density of repolarizing I K1 (and I KAch ) and results in generation of propagating AP (Varghese 2016).…”