Noradrenaline up‐regulates volume‐regulated chloride current by PKA‐independent cAMP/exchange protein activated by cAMP pathway in human atrial myocytes

Abstract

These data show that I evoked by cell swelling of human atrial myocytes is up-regulated by noradrenaline via a PKA-independent cAMP/Epac pathway in human atrial myocytes. cAMP/Epac-induced I is expected to shorten action potential duration during human atrial myocytes swelling and may be involved in abnormal cardiac electrical activity during cardiac pathologies that evoke β-adrenoceptor signalling.

A Swelling-Activated Chloride Current in Microglial Cells is Suppressed by Epac and Facilitated by PKA – Impact on Phagocytosis

“…Thus, in addition to the classical hallmarks of I Cl,swell , the present and a previous study suggest that I Cl,swell is modulated by cAMP-dependent pathways [37]. Moreover, it has recently been shown, that I Cl,swell of human atrial myocytes is augmented by NA, an effect mimicked by the Epac agonist 8-pCPT-2-O-Me-cAMP and inhibited by an Epac antagonist, thus implying that the effect of NA is mediated by an Epac-dependent pathway in these cells [50]. This contrasts the finding of our present study showing an inhibition of I Cl,swell by NA and 8-pCPT-2-O-Me-cAMP.…”

Cardiac transmembrane ion channels and action potentials: cellular physiology and arrhythmogenic behavior

“…This should be taken into consideration when drugs are studied in rabbit atrial preparations, and it highlights the importance of species-dependent electrophysiological differences. A distinct, cellular swelling-induced Cl À current has also been described in human atrial myocytes (554), which is also modulated by PKA-independent, cAMP-mediated b-adrenoceptor signaling (555). The existence and potential role of Na v 1.8 channels in I NaLate in the atria represents an interesting issue; however, it is still the subject of debate (556) and requires further studies.…”

“…Neurohor-monal modulation of the atria is particularly important. Acetylcholine (358,563), catecholamines (555,563), substance P (297), adenosine (564,565), and serotonin (566) have been reported to influence atrial action potential and its underlying currents. In the atria, I K,ACh is robust and even has a small but persistent constitutively active component, which operates without parasympathetic stimulation and seems greatly augmented during chronic AF (358).…”

New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling

“…These channels are depolarizing in beta cells and are activated not only by cell swelling as a consequence of elevated glucose, but also by cAMP and the sulfonylurea glyburide [200]. Which arm of the cAMP signaling pathway regulates these channels in beta cells is unknown but in other cells both positive and negative effects of Epac on channel activity have been reported along with a positive effect or no effect of PKA [201,202]. It was recently shown that VRAC-forming LRRC8 plays a role in glucose sensing and the regulation of insulin secretion from beta cells [203].…”