Role of Nitric Oxide in Activity Control of Mechanically Gated Ionic Channels in Cardiomyocytes: NO-Donor Study

Abstract

Whole-cell ionic currents through mechanically gated channels (MGC) were recorded in isolated cardiomyocytes under voltage clamp conditions. In unstrained cells, NO donors SNAP and DEA-NO activated MGC and induced MG-like currents. In contrast, in stretched cells with activated MGC, these NO-donors inactivated and inhibited MGC.

IL-1 provokes electrical abnormalities in rat atrial myocardium

“…to find proper answer we took into account the fact that stretch induced signal transducer and activator of transcription (STAT) phosphorylation [18], as a mediator in intracellular NO production [19], represents an enhancer of the process of transformation of stretch induced hump-like depolarizations into single extra-APs [20]. Based on that and on the fact that stretch elimination turned short sections of tachy-arrhythmia into normal rhythm, we outlined that the induced alteration of the MGCs by stretch in the presence of the IL-1α, is mainly regulated via stretch increased NO production [20], while the direct ionotropic effect of the IL-1α [3] during stretching is not pronounced.…”

The Role of Proinflammatory Cytokines in Regulation of Cardiac Bioelectrical Activity: Link to Mechanoelectrical Feedback

“…Moreover, IL-6 regulated the contractility and the direct negative inotropic effect of IL-6 is mediated through a myocardial nitric oxide synthase. This data and studies reporting that NO directly regulates activity of mechanically gated channels (MGCs) (Kazanski et al, 2010a(Kazanski et al, , b, 2011 allowed us to suppose that in heart IL-6 would be an effective regulator of MGCs activity and therefore will regulate mechanoelectrical feedback.…”

“…Since TNF-α activates NO synthases of cardiomyocytes (Finkel et al, 1992;Goldhaber et al, 1996;Nakayama et al, 2009;Bougaki et al, 2010) and rise of the concentration of the intracellular NO activates MGCs (Kazanski et al, 2010a(Kazanski et al, , b, 2011, which allows Na ions entry into the cell leading to cellular depolarization and shift of resting potential to E C we proposed, that TNF-α induced arrhythmias can be linked with MGCs activation. This is the most simple mechanism, explaining the appearance of arrhythmias after TNF-α application.…”

“…Experimental data in this study was obtained from the isolated ventricular myocytes of mouse, rat and guinea pig by means of patch-clamp method in whole-cell configuration. The data demonstrated that NO donors lead to MGCs activation and appearance of MG-like currents in undeformed ventricular myocytes, whereas, it can also lead to the inactivation of the stretched cells with activation MGCs and inhibit the conductivity of these channels (Kazanski et al, 2010a(Kazanski et al, , 2011. NO scavenger PTIO causes inactivation of all MGCs.…”

Effects of interleukin-6 on the bio-electric activity of rat atrial tissue under normal conditions and during gradual stretching

“…Nevertheless, the particular mechanisms mediating the increase in NO production induced by IL-6 are not clearly understood at present. In the heart, constitutive NO synthases plays a key role in the NO level regulation (Kazanski et al, 2010a). Therefore, IL-6 may alter the level of NO by changing the level of expression of constitutive NO synthases.…”