RT Journal Article
T1 Endocannabinoids and cannabinoid analogues block human cardiac Kv4.3 channels in a receptor-independent manner
A1 Amorós García, Irene
A1 Barana Muñoz, Adriana
A1 Caballero Collado, Ricardo
A1 Gómez García, Ricardo
A1 Osuna, Lourdes
A1 Lillo, María Pilar
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
AB Endocannabinoids are amides and esters of long chain fatty acids that can modulate ion channels through both receptor-dependent and receptor-independent effects. Nowadays, their effects on cardiac K(+) channels are unknown even when they can be synthesized within the heart. We have analyzed the direct effects of endocannabinoids, such as anandamide (AEA), 2-arachidonoylglycerol (2-AG), the endogenous lipid lysophosphatidylinositol, and cannabinoid analogues such as palmitoylethanolamide (PEA), and oleoylethanolamide, as well as the fatty acids from which they are endogenously synthesized, on human cardiac Kv4.3 channels, which generate the transient outward K(+) current (I(to1)). Currents were recorded in Chinese hamster ovary cells, which do not express cannabinoid receptors, by using the whole-cell patch-clamp. All these compounds inhibited I(Kv4.3) in a concentration-dependent manner, AEA and 2-AG being the most potent (IC(50) approximately 0.3-0.4 microM), while PEA was the least potent. The potency of block increased as the complexity and the number of C atoms in the fatty acyl chain increased. The effects were not mediated by modifications in the lipid order and microviscosity of the membrane and were independent of the presence of MiRP2 or DPP6 subunits in the channel complex. Indeed, effects produced by AEA were reproduced in human atrial I(to1) recorded in isolated myocytes. Moreover, AEA effects were exclusively apparent when it was applied to the external surface of the cell membrane. These results indicate that at low micromolar concentrations the endocannabinoids AEA and 2-AG directly block human cardiac Kv4.3 channels, which represent a novel molecular target for these compounds.
PB Elsevier
SN 0006-2952
YR 2010
FD 2010-01-01
LK https://hdl.handle.net/20.500.14352/100151
UL https://hdl.handle.net/20.500.14352/100151
LA eng
NO Amorós I, Barana A, Caballero R, Gómez R, Osuna L, Lillo MP, Tamargo J, Delpón E. Endocannabinoids and cannabinoid analogues block human cardiac Kv4.3 channels in a receptor-independent manner. J Mol Cell Cardiol. 2010 Jan;48(1):201-10. doi: 10.1016/j.yjmcc.2009.07.011
NO Instituto de Salud Carlos III
NO Ministerio de Educación y Ciencia
NO Fundación LILLY
NO Centro Nacional de Investigaciones Cardiovasculares
NO Universidad Complutense de Madrid
NO Sociedad Española de Cardiología
DS Docta Complutense
RD 31 dic 2025