Cardiovascular perspectives of the TRP channel polycystin 2

Abstract

Calcium release from the endoplasmic reticulum (ER) is predominantly driven by two key ion channel receptors, inositol 1, 4, 5‐triphosphate receptor (InsP3R) in non‐excitable cells and ryanodine receptor (RyR) in excitable and muscle‐based cells. These calcium transients can be modified by other less‐studied ion channels, including polycystin 2 (PC2), a member of the transient receptor potential (TRP) family. PC2 is found in various cell types and is evolutionarily conserved with paralogues ranging from single‐cell organisms to yeasts and mammals. Interest in the mammalian form of PC2 stems from its disease relevance, as mutations in the PKD2 gene, which encodes PC2, result in autosomal dominant polycystic kidney disease (ADPKD). This disease is characterized by renal and liver cysts, and cardiovascular extrarenal manifestations. However, in contrast to the well‐defined roles of many TRP channels, the role of PC2 remains unknown, as it has different subcellular locations, and the functional understanding of the channel in each location is still unclear. Recent structural and functional studies have shed light on this channel. Moreover, studies on cardiovascular tissues have demonstrated a diverse role of PC2 in these tissues compared to that in the kidney. We highlight recent advances in understanding the role of this channel in the cardiovascular system and discuss the functional relevance of PC2 in non‐renal cells. image

Utilization of the genetically encoded calcium indicator Salsa6F in cardiac applications

“…To assess feasibility of using the Salsa6f in transgenic mouse lines targeting genes that modify calcium handling, we crossed the Salsa6f mouse with a floxed Pkd2 mouse. The gene Pkd2 encodes the protein Polycystin-2, a non-selective cation TRP channel that localizes to the SR where it can mediate calcium transients via regulation of the ryanodine receptor and the L-type calcium channel [15]. Application of the Salsa6f model in a heterozygous and homozygous mouse model of cardiac PC2-KO demonstrates the feasibility of using the Salsa6f to measure cardiac calcium transients in transgenic models.…”

Channelling calcium signals to therapeutics

“…Interestingly, polycystin 2 (PC2) is an intracellular Ca 2+ channel and member of the TRP superfamily. As PC2 is best known for its ability to cause polycystic kidney disease, Marquez‐Nogueras and Kuo (2024) focus on the contributions of PC2 in cardiovascular tissues. PC2 is one of many intracellular channels; the TRPML family of channels are found primarily within the endolysosomal system, where structurally distinct two‐pore channels (TPCs) are also found.…”