Adrenergic prolongation of action potential duration in rainbow trout myocardium via inhibition of the delayed rectifier potassium current, IKr.

Denis V. Abramochkin, Thomas Eliot Haworth, Vladislav S. Kuzmin, Irina Dzhumaniiazova, Ksenia B. Pustovit, Maeva Gacoin, Holly Shiels

Research output: Contribution to journalArticlepeer-review

Abstract

Catecholamines mediate the ‘fight or flight’ response in a wide variety of vertebrates.
The endogenous catecholamine adrenaline increases heart rate and contractile
strength to raise cardiac output. The increase in contractile force is driven in large part
by an increase in myocyte Ca 2+ influx on the L-type Ca current (I CaL ) during the
cardiac action potential (AP). Here, we report a K + - based mechanism that prolongs
AP duration (APD) in fish hearts following adrenergic stimulation. We show that
adrenergic stimulation inhibits the delayed rectifier K + current (I Kr ) in rainbow trout
( Oncorhynchus mykiss ) cardiomyocytes. This slows repolarization and prolongs
APD which may contribute to positive inotropy following adrenergic stimulation in fish
hearts. The endogenous ligand, adrenaline (10 -6 M), which activates both α- and βARs reduced maximal I Kr tail current to 61.4±3.9% of control in atrial and ventricular
myocytes resulting in an APD prolongation of ~ 20% at both 50 and 90%
repolarization. This effect was reproduced by the α-specific adrenergic agonist,
phenylephrine (10 -6 M), but not the β-specific adrenergic agonist isoproterenol (10 -
6 M). Adrenaline (10 -6 M) in the presence of β 1 and β 2 -blockers (10 -6 M
atenolol and 10 -6 M ICI-118551, respectively) also inhibited I Kr . Thus, I Kr
suppression following adrenergic stimulation leads to APD prolongation in the rainbow
trout heart. This is the first time this mechanism has been identified in fish and may act
in unison with the well-known enhancement of I CaL following adrenergic stimulation
to prolong APD and increase cardiac inotropy.
Original languageEnglish
JournalComparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology
Publication statusAccepted/In press - 4 Feb 2022

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