Connexin-43 hemichannels opened by metabolic inhibition.
The cause of altered ionic homeostasis leading to cell death during ischemia and metabolic inhibition is unclear. Hemichannels, which are precursors to gap junctions, are nonselective ion channels that are permeable to molecules of less than Mr 1000. We show that hemichannels open upon exposure to calcium-free solutions when they are either heterologously overexpressed in HEK293 cells or endogenously expressed in cardiac ventricular myocytes. In the presence of normal extracellular calcium, hemichannels open during metabolic inhibition. During ischemia and other forms of metabolic inhibition, activation of relatively few hemichannels will seriously compromise the cell's ability to maintain ionic homeostasis, which is an essential step promoting cell death.
John
S A
SA
Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Kondo
R
R
Wang
S Y
SY
Goldhaber
J I
JI
Weiss
J N
JN
D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D015640:Ion Channel Gating; D008164:Luminescent Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism
D018031:Connexin 43; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins