TRP Channels in Cardiac Arrhythmia: Their Role During Purinergic Activation Induced by Ischemia

TRPC channels, an overarching Ca2+ paradigm in the developing heart

“…In the embryonic chick heart, Ca 2+ channel density is maximal at 3 days and decreases at 17 days 3 , whereas Ca 2+ channel density is low in the foetal heart and increases with development in guinea-pig 4 , rabbit 5 and human 6 , consistent with the need for additional Ca 2+ entry through other sarcolemmal voltage-dependent proteins such as the T-type Ca 2+ channel, the Cav1.3 L-type Ca 2+ channel, and the Na/Ca 2+ exchanger 2,[6][7][8] . Other candidate channels suspected to provide Ca 2+ entry into the immature myocyte have been associated with voltage-independent channels, canonical transient receptor potential (TRPC) channels 9 . TRPC channels are composed of 4 subunits with each containing 6 membrane-spanning regions lacking the voltage sensors in the fourth domain (thus voltageindependent).…”

“…TRPC channels possess multiple regulatory and protein interaction sites, a property that allows them to associate and form homotetramers or heterotetramers. TRPC channels are activated following stimulation of receptors coupled to phospholipase C pathways through inositol trisphosphate and diacylglycerol (receptor-operated channels or ROCs), by depletion of internal calcium stores (store-operated channels or SOCs ), and by membrane stretching (stretch-activated channels) 9 . The functional role of TRPC channels in the immature heart is just emerging.…”