TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: Co-localization at z-discs, costameres and intercalated discs

Abstract

Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid subtype-1 (TRPV1) are structurally related, non-selective cation channels that show a high permeability to calcium. Previous studies indicate that TRP channels play a prominent role in the regulation of cardiovascular dynamics and homeostasis, but also contribute to the pathophysiology of many diseases and disorders within the cardiovascular system. However, no studies to date have identified the functional expression and/or intracellular localization of TRPA1 in primary adult mouse ventricular cardiomyocytes (CMs). Although TRPV1 has been implicated in the regulation of cardiac function, there is a paucity of information regarding functional expression and localization of TRPV1 in adult CMs. Our current studies demonstrate that TRPA1 and TRPV1 ion channels are co-expressed at the protein level in CMs and both channels are expressed throughout the endocardium, myocardium and epicardium. Moreover, immunocytochemical localization demonstrates that both channels predominantly colocalize at the Z-discs, costameres and intercalated discs. Furthermore, specific TRPA1 and TRPV1 agonists elicit dose-dependent, transient rises in intracellular free calcium concentration ([Ca2+]i) that are abolished in CMs obtained from TRPA1−/− and TRPV1−/− mice. Similarly, we observed a dose-dependent attenuation of the TRPA1 and TRPV1 agonist-induced increase in [Ca2+]i when WT CMs were pretreated with increasing concentrations of selective TRPA1 or TRPV1 channel antagonists. In summary, these findings demonstrate functional expression and the precise ultrastructural localization of TRPA1 and TRPV1 ion channels in freshly isolated mouse CMs. Crosstalk between TRPA1 and TRPV1 may be important in mediating cellular signaling events in cardiac muscle.

Transient receptor potential vanilloid 1 inhibitors block laparotomy‐ and opioid‐induced infarct size reduction in rats

“…If cardiac protection was neuron mediated, the ability for ischaemic preconditioning to reduce myocardial infarct size should not be abolished in an isolated heart model. We and others recently identified that TRPV1 is present and functional within the cardiac myocyte (Andrei et al, 2016;Hurt et al, 2016). TRPV1 also modulates myocardial ischaemiareperfusion injury through the regulation of mitochondrial membrane potential (Hurt et al, 2016).…”

TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway

“…8 To our knowledge, the current study is the first to thoroughly characterize the effects of TRPA1 stimulation on [Ca 2C ] i and contractile function in electrically-stimulated adult mouse CMs. The major finding of the current study is that TRPA1 agonist, AITC, stimulates dose-dependent increases in peak [Ca ] i and contractile function were qualitatively and quantitatively similar to the classical CM responses observed following b-AR stimulation with ISO, we did not observe any increase in CM cAMP production or PKA activity following TRPA1 activation with AITC, and the PKA inhibitor peptide was without effect on AITC induced modifications in CM [Ca 2C ] i and contractile function.…”

“…[5][6][7] We recently reported for the first time the expression of TRPA1 at the protein level in cardiac muscle and it's co-localization with TRPV1 ion channels at the costamere, z-disk and intercalated discs in murine cardiomyocytes (CM). 8 However, the extent to which TRPA1 ion channel stimulation plays a role in the regulation and/or modulation of CM contractile function have not been previously reported. In the current study, we tested the hypothesis that stimulation of TRPA1 ion channels in electrically-stimulated mouse ventricular CMs results in increases in peak intracellular free Ca 2C concentration ([Ca 2C ] i ) and a concomitant increase in CM contractile function.…”

“…8 In brief, mice were killed by cervical dislocation and hearts were collected into a bath of perfusion buffer. Hearts were cannulated via the aorta and blood was flushed with 0.2 mL perfusion buffer.…”

TRPA1 and TRPV1 contribute to propofol-mediated antagonism of U46619-induced constriction in murine coronary arteries

“…It is well established in sensory neurons [11, 13] and in other tissue types [36] that receptor activation with capsaicin (specific TRPV1 agonist) or allyl isothiocyanate (TRPA1 agonist) results in channel activation and a transient influx of Ca 2+ leading to an increase in intracellular free Ca 2+ concentration [Ca 2+ ] i . Although there is no evidence of propofol-induced TRPV1-mediated calcium-influx, we previously demonstrated that propofol induces a transient increase in [Ca 2+ ] i via a TRPA1-dependent pathway in sensory neurons [11].…”