Voltage-dependent potassium channels are spanning-membrane integral proteins involved in several and diverse physiological and pathological processes such as immune response or cardiovascular function. KV7.1 channel with the KCNE1 regulatory subunit form one of the most important current of the repolarization phase of the cardiac action potential (IKs). We analyzed, using the patch-clamp technique, the acute and chronic exposition of polyunsaturated fatty acids (PUFAs), DHA and AA, in KV7.1/KCNE1 channels expressed in COS-7 cells. Acute DHA and AA exposition increased the magnitude of KV7.1/KCNE1 currents. DHA but not AA slowed the activation kinetics. However, both PUFAs accelerated the deactivation kinetics. Chronic exposition to these compounds did not modify the magnitude of the currents. However, DHA shifted the activation curve toward more negative membrane potentials and accelerated the activation and deactivation kinetics of the channels. On the contrary, AA slowed the activation whereas it accelerated the deactivation process. PUFAs effects on KV7.1/KCNE1 channels depends on both the compound’s chemical nature, n-3 or n-6 PUFAs, as well as the time of exposure, which might be acute or chronic. It has been described that enriched PUFAs diet has anti-inflammatory properties. Moreover, n-3 or n-6 PUFAs lipidderived mediators such as lipoxins and resolvins (which levels are increased by the consumption of aspirin), have been emerged as potent anti-inflammatory agents that promote the resolution phase of the inflammation process. Ion channels, and specially potassium ion channels, play an essential role in macrophages physiology. Accordingly, we also studied the lipid-derived mediators effects on both bone marrow derived macrophages (BMDM), which LPSdependent activation are related with the increased of KV1.3/KV1.5 expression, and in KV7.1/KCNE1 channels where the PUFAs effects have been studied. Lipoxins, but not resolvins, could reverse the LPS-activated macrophages. However, resolvins KV7.1/KCNE1 block were much more potent.

Resumen del trabajo presentado al VI Meeting de la Red Española de Canales Ióniocs (RECI), celebrado en Santiago de Compostela del 6 al 8 de septiembre de 2017.

Funded by SAF2013-45800-R, SAF2016-75021-R, BFU2014-54928-R and CIBERCV (FIS CB/11/00222).

Peer reviewed