Why the study?
Does 7-OH-DPAT affect cardiac action potential duration and IKr channels in preclinical models?
Does 7-OH-DPAT affect cardiac action potential duration and IKr channels in preclinical models?
The D3-dopaminergic agonist 7-OH-DPAT directly prolongs cardiac action potential duration by blocking the IKr potassium channel, an effect independent of D3 receptor activation.
Potential proarrhythmic effects of 7-OH-DPAT merit caution in development; leaves open translation to human electrophysiology and D3-independent mechanisms.
The D3-dopaminergic agonist (+/-) 7-hydroxy-dipropylaminotetralin (7-OH-DPAT) prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced the upstroke velocity of the action potential of rabbit sinoatrial node cells. These effects were not mediated by D3-dopaminergic receptors. In cat Purkinje fibers, the drug increased action potential duration. In voltage-clamped cat ventricular myocytes, 7-OH-DPAT blocked the rapid component of the delayed rectifier potassium current, IKr. This effect was corroborated in experiments studying the effect of the drug on human Ether-a-go-go-related Gene channels expressed in Xenopus oocytes and in HEK293 cells. We conclude that the direct electrophysiologic effects of 7-OH-DPAT on cardiac tissues are caused by the blockade of the rapid component of the delayed rectifier potassium current, IKr.
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Torres-Jácome et al. (2006) studied this question.
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