Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Bondarenko, AI; Panasiuk, O; Okhai, I; Montecucco, F; Brandt, KJ; Mach, F.
Ca²⁺-dependent potassium channels and cannabinoid signaling in the endothelium of apolipoprotein E knockout mice before plaque formation.
J Mol Cell Cardiol. 2018; 115: 54-63. Doi: 10.1016/j.yjmcc.2018.01.002
Web of Science PubMed FullText FullText_MUG

Leading authors Med Uni Graz: Bondarenko Oleksandr
Co-authors Med Uni Graz: Panasiuk Olga
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Endothelial Ca²⁺-dependent K⁺ channels (K_Ca) regulate endothelial function. We also know that stimulation of type 2 cannabinoid (CB₂) receptors ameliorates atherosclerosis. However, whether atherosclerosis is accompanied by altered endothelial K_Ca- and CB₂ receptor-dependent signaling is unknown. By utilizing an in situ patch-clamp approach, we directly evaluated the K_Ca channel function and the CB₂ receptor-dependent electrical responses in the endothelium of aortic strips from young ApoE^-/- and C57Bl/6 mice. In the ApoE^-/- group, the resting membrane potential (-30.1±1.1mV) was less negative (p<0.05) compared to WT (-38.9±1.4mV) and voltage ramps generated an overall K_Ca current of reduced amplitude. The peak hyperpolarization to 2μM Ach was not different between the groups. However, the sustained component was significantly reduced in ApoE^-/- strips. In contrast, the peak hyperpolarization to 0.2μM Ach was increased in the ApoE^-/- group, and SKA-31, a direct IK_Ca/SK_Ca channel opener, produced a hyperpolarization and whole-cell current of greater amplitude. The BK_Ca opener NS1619 produced hyperpolarization that was enhanced in ApoE^-/- group. N-arachidonoyl glycine, a BK_Ca opener, produced a hyperpolarization of enhanced amplitude in ApoE^-/- arteries. Selective CB₂ receptor agonist AM1241 (5μM) had no effect on endothelial membrane potential in WT group; however, in ApoE^-/- group, it elicited hyperpolarization that was inhibited by a selective CB₂ receptor antagonist AM630. Conclusively, our data point to functional down-regulation of basal IK_Ca activity in unstimulated endothelium of ApoE^-/- mice. Direct and indirect IK_Ca stimulation resulted in increased recruitment of the channels. In addition, our data point to up-regulation of endothelial BK_Ca channels and CB₂ receptors in ApoE^-/- arteries.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; Aorta - metabolism; Apolipoproteins E - deficiency, metabolism; Arachidonic Acids - pharmacology; Benzimidazoles - pharmacology; Benzothiazoles - pharmacology; Calcium - metabolism; Cannabinoids - metabolism, pharmacology; Endothelial Cells - metabolism; Endothelium, Vascular - metabolism, pathology; Glycine - analogs & derivatives, pharmacology; Ion Channel Gating - drug effects; Mice, Inbred C57BL - administration & dosage; Mice, Knockout - administration & dosage; Plaque, Atherosclerotic - metabolism, pathology; Potassium Channels - metabolism; Signal Transduction - administration & dosage; Up-Regulation - drug effects
Find related publications in this database (Keywords): Atherosclerosis; Endothelial cells; Potassium channels; Cannabinoids receptor type 2