The endocannabinoid ARA-S facilitates the activation of cardiac Kv7.1/KCNE1 channels from different species

The endocannabinoid ARA-S facilitates the activation of cardiac Kv7.1/KCNE1 channels from different species

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The endogenous endocannabinoid-like compound N-arachidonoyl-L-serine (ARA-S) facilitates activation of the human Backpack Kv7.1/KCNE1 channel and shortens a prolonged action potential duration and QT interval in guinea pig hearts.Hence, ARA-S is interesting to study further in cardiac models to explore the functional impact of such Kv7.1/KCNE1-mediated effects.To guide which animal models would be suitable for assessing ARA-S effects, and to aid interpretation of findings in different experimental models, it is useful to know whether Kv7.

1/KCNE1 channels from relevant species respond similarly to ARA-S.To this end, we used the two-electrode voltage clamp technique to compare the effects of ARA-S on Kv7.1/KCNE1 channels from guinea pig, rabbit, and human Kv7.1/KCNE1, when expressed in Xenopus laevis oocytes.We found that the activation of Kv7.

1/KCNE1 channels from all tested species was facilitated by ARA-S, seen as a concentration-dependent shift in the voltage-dependence of channel opening and increase in current amplitude and conductance over a broad voltage range.The rabbit channel displayed quantitatively similar effects as the human channel, whereas the guinea pig channel responded with more U-matic Blank Video Tape prominent increase in current amplitude and maximal conductance.This study suggests that rabbit and guinea pig models are both suitable for studying ARA-S effects mediated via Kv7.1/KCNE1.