Na(+) entry and modulation of Na(+)/Ca(2+) exchange as a key mechanism of TRPC signaling.
Ion channels formed by canonical transient receptor potential (TRPC) proteins are considered to be key players in cellular Ca(2+) homeostasis. As permeation of Ca(2+) through TRPC homo- and/or heteromeric channels has been repeatedly demonstrated, analysis of the physiological role of TRPC proteins was so far based on the concept that these proteins form regulated Ca(2+) entry channels. The well-recognized lack of cation selectivity of TRPC channels and the ability to generate substantial monovalent conductances that govern membrane potential and cation gradients were barely appreciated as a physiologically relevant issue. Nonetheless, recent studies suggest monovalent, specifically Na(+) permeation through TRPC cation channels as an important event in TRPC signaling. TRPC-mediated Na(+) entry may be converted into a distinct pattern of cellular Ca(2+) signals by interaction with Na(+)/Ca(2+) exchanger proteins. This review discusses current concepts regarding the link between Na(+) entry through TRPC channels and cellular Ca(2+) signaling.
Eder
Petra
P
Institute of Pharmaceutical Sciences, Pharmacology and Toxicology, Karl-Franzens-University of Graz, Universitaetsplatz 2, 8010 Graz, Austria.
Poteser
Michael
M
Romanin
Christoph
C
Groschner
Klaus
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D008954:Models, Biological; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D050052:TRPC Cation Channels / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C110374:sodium-calcium exchanger 1; D012964:Sodium; D002118:Calcium