Hydrogen sulphide increases pulmonary veins and atrial arrhythmogenesis with activation of protein kinase C

Abstract

Hydrogen sulphide (H2S), one of the most common toxic air pollutants, is an important aetiology of atrial fibrillation (AF). Pulmonary veins (PVs) and left atrium (LA) are the most important AF trigger and substrate. We investigated whether H2S may modulate the arrhythmogenesis of PVs and atria. Conventional microelectrodes and whole‐cell patch clamp were performed in rabbit PV, sinoatrial node (SAN) or atrial cardiomyocytes before and after the perfusion of NaHS with or without chelerythrine (a selective PKC inhibitor), rottlerin (a specific PKC δ inhibitor) or KB‐R7943 (a NCX inhibitor). NaHS reduced spontaneous beating rates, but increased the occurrences of delayed afterdepolarizations and burst firing in PVs and SANs. NaHS (100 μmol/L) increased IKATP and INCX in PV and LA cardiomyocytes, which were attenuated by chelerythrine (3 μmol/L). Chelerythrine, rottlerin (10 μmol/L) or KB‐R7943 (10 μmol/L) attenuated the arrhythmogenic effects of NaHS on PVs or SANs. NaHS shortened the action potential duration in LA, but not in right atrium or in the presence of chelerythrine. NaHS increased PKC activity, but did not translocate PKC isoforms α, ε to membrane in LA. In conclusion, through protein kinase C signalling, H2S increases PV and atrial arrhythmogenesis, which may contribute to air pollution‐induced AF.

Transsulfuration metabolites and the association with incident atrial fibrillation – An observational cohort study among Norwegian patients with stable angina pectoris

“…Transsulfuration primarily takes place in hepatocytes; however some studies suggest that it also can take place in human blood as endothelial cells have been shown to secrete CBS. Hydrogen sulfide (H 2 S) is produced during transsulfuration and has been linked to pulmonary vein and atrial arrhythmogenesis in rats [21,22]. By remethylation, Hcy is a precursor of S-adenosylmethionine (SAM), which is crucial for remethylation reactions.…”

Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms

“…The PKC-mediated increases in I KATP and I NCX were also observed in atrial myocytes; however, such effects were only presented in left atrial myocytes but not right atrial myocytes. This interesting observation demonstrates that H 2 S can lead to increased interatrial dispersion, and therefore increases the risk of supraventricular arrhythmias (145). Noted that PKC may also regulate other channels in addition to I KATP and I NCX , such as I to (146), I NaL (147), I Ks (148), and their potential roles in H 2 S-induced arrhythmias warrants further investigation.…”

“…The mechanism of proarrhythmic effects of H 2 S can be more complicated in the atria. Recently, Chan et al performed a comprehensive investigation on the influences of H 2 S on the atria and provided novel insights into the proarrhythmic effects of H 2 S (145). The study reported that NaHS (H 2 S donor) significantly reduced sinoatrial node (SAN) beating rates, causing SAN dysfunction and potentially the AF.…”

ZFHX3 knockdown dysregulates mitochondrial adaptations to tachypacing in atrial myocytes through enhanced oxidative stress and calcium overload

“…Micropipettes were filled with a solution containing KCl (140 mmol L −1 ), MgCl 2 (1.0 mmol L −1 ), HEPES (10 mmol L −1 ), EGTA (5 mmol L −1 ) and GTP (0.1 mmol L −1 ; pH adjusted to 7.3 with KOH). I KATP was elicited through depolarization in 10‐mV steps from a holding potential of −40 mV to test potentials between −100 and +100 mV for 300 ms at a frequency of 0.5 Hz 58 …”