Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis

Abstract

The sarcolemmal ATP-sensitive K+ (sarcKATP) channel plays a cardioprotective role during stress. However, the role of the sarcKATP channel in the apoptosis of cardiomyocytes and association with mitochondrial calcium remains unclear. For this purpose, we developed a model of LPS-induced sepsis in neonatal rat cardiomyocytes (NRCs). The TUNEL assay was performed in order to detect the apoptosis of cardiac myocytes and the MTT assay was performed to determine cellular viability. Exposure to LPS significantly decreased the viability of the NRCs as well as the expression of Bcl-2, whereas it enhanced the activity and expression of the apoptosis-related proteins caspase-3 and Bax, respectively. The sarcKATP channel blocker, HMR-1098, increased the apoptosis of NRCs, whereas the specific sarcKATP channel opener, P-1075, reduced the apoptosis of NRCs. The mitochondrial calcium uniporter inhibitor ruthenium red (RR) partially inhibited the pro-apoptotic effect of HMR-1098. In order to confirm the role of the sarcKATP channel, we constructed a recombinant adenovirus vector carrying the sarcKATP channel mutant subunit Kir6.2AAA to inhibit the channel activity. Kir6.2AAA adenovirus infection in NRCs significantly aggravated the apoptosis of myocytes induced by LPS. Elucidating the regulatory mechanisms of the sarcKATP channel in apoptosis may facilitate the development of novel therapeutic targets and strategies for the management of sepsis and cardiac dysfunction.

Upregulation of UCP2 Expression Protects against LPS-Induced Oxidative Stress and Apoptosis in Cardiomyocytes

“…Oxidative stress and apoptosis are considered important events of LPS-induced myocardial injury [43, 44]. Although Zheng et al [37] reported that silencing of UCP2 by siRNA aggravated the damage to mitochondrial morphology and function in cardiomyocytes, the mechanism of UCP2 in LPS-induced myocardial injury has not been fully elucidated.…”

Proteomics and Transcriptomics Analysis Reveals Clues into the Mechanism of the Beneficial Effect of Electrical Stimulation on Rat Denervated Gastrocnemius Muscle

“…In this study, potassium voltage-gated channel subfamily J member 11 (KCNJ11), which is associated with this module, was found to be down-regulated after denervation and up-regulated after electrical stimulation. KCNJ11 is an ATP-sensitive K+ channel, and has been reported to play a cardioprotective role during stress and to participate in apoptosis in cardiomyocytes [39]. However, its function in the skeletal muscle has not been studied, and our results suggest that it may be involved in the anti-apoptosis function of electrical stimulation.…”

Carvacrol treatment opens Kir6.2 ATP-dependent potassium channels and prevents apoptosis on rat testis following ischemia–reperfusion injury model

“…Similarly, Tsounapi et al reported that Kir6.2 was opened after Cromakalim administration and prevented apoptosis in rat testicular IR model [ 25 ]. In another study, sarcolemmal (sarc)KATP channel was opened via P-1075 and it reduced lipopolysaccharide-induced apoptosis, while blocking sarcKATP channel with HMR-1098 increased lipopolysaccharide-induced apoptosis in cultured neonatal rat cardiomyocyte cells [ 50 ]. Oliveira et al described that Carvacrol mediates the release of endogenous prostaglandins on an experimental gastric lesion model in rodent, which has a gastroprotective role by causing increased mucus production, opening of KATP channels, activation of nitric oxide (NO) synthase [ 51 ].…”