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Review
. 2020 Jan 10;9(1):173.
doi: 10.3390/cells9010173.

TRPC Channels: Dysregulation and Ca2+ Mishandling in Ischemic Heart Disease

Débora Falcón  1   2 , Isabel Galeano-Otero  1 , Marta Martín-Bórnez  1 , María Fernández-Velasco  2   3 , Isabel Gallardo-Castillo  4 , Juan A Rosado  5 , Antonio Ordóñez  2 , Tarik Smani  1   2
Affiliations
Review

TRPC Channels: Dysregulation and Ca2+ Mishandling in Ischemic Heart Disease

Débora Falcón et al. Cells. .

Abstract

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP channels, TRPC channels may form homo or heterotetrameric ion channels, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase in the expression of different TRPC isoforms was observed in different animal models of heart infarcts and in vitro experimental models of ischemia and reperfusion. TRPC channel-mediated increase of the intracellular Ca2+ concentration seems to be required for the activation of the signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion and to heart infarction.

Keywords: Ca2+ entry; TRPC channel; cardiac infarction; cardiac repair.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Scheme summarizing transient receptor potential canonical (TRPC) channel isoforms dysregulated under myocardial infarction (MI) and ischemia and reperfusion. TRPC1, 3, 4, 5, and 6 are upregulated in mouse and rat animal models of MI [5,13,71]. Compelling evidence indicates that TRPC channel overexpression contributes to Ca2+ entry, mediating the activation of Ca2+-sensitive signaling pathways, such as calcineurin–NFAT, a critical pathway involved in apoptosis, cardiac hypertrophy, and fibrosis [13,28,55,66,67]. TRPC proteins are likely also involved in cardiac repair-related processes. The protective role played by TRPC6 in wound healing is of note [37]. Other studies suggested a role of TRPC channels, such as TRPC5, in angiogenesis and revascularization triggered post ischemia [104].
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