Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes.
A large conductance (∼300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca(2+) release from the sarcoplasmic reticulum, particularly when augmented by caffeine, has been described previously in isolated cardiac myocytes. A potential candidate for this channel is pannexin 1 (Panx1), which has been shown to form large ion channels when expressed in Xenopus oocytes and mammalian cells. Panx1 function is implicated in ATP-mediated auto-/paracrine signaling, and a crucial role in several cell death pathways has been suggested. Here, we demonstrate that after culturing for 4 days LCC activity is no longer detected in myocytes but can be rescued by adenoviral gene transfer of Panx1. Endogenous LCCs and those related to expression of Panx1 share key pharmacological properties previously used for identifying and characterizing Panx1 channels. These data demonstrate that Panx1 constitutes the LCC of cardiac myocytes. Sporadic openings of single Panx1 channels in the absence of Ca(2+) release can trigger action potentials, suggesting that Panx1 channels potentially promote arrhythmogenic activities.
Department of Cellular Physiology, Ruhr-University Bochum, 44780 Bochum, Germany. cecile-kienitz@rub.de
Marie-Cecile
MC
Kienitz
Kirsten
K
Bender
Rolf
R
Dermietzel
Lutz
L
Pott
Georg
G
Zoidl
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001696:Biomechanical Phenomena; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D017630:Connexins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C479936:pannexin 1, rat; D000255:Adenosine Triphosphate