A role for annexin IV in epithelial cell function. Inhibition of calcium-activated chloride conductance.
The cellular function of annexin IV was evaluated by correlating tissue expression, cellular localization, and whole-cell electrophysiology. Immunolocalization and biochemical data demonstrate that annexin IV is concentrated along the apical membranes of many epithelia. Introduction of purified exogenous annexin IV into colonic T84 cells through a patch pipette specifically prevented Ca(2+)-dependent Cl- current activation. Affinity-purified antibody against annexin IV applied in the same manner enhanced the activation. Reduction of the endogenous level of annexin IV with a derivatized oligodeoxynucleotide antisense to annexin IV mRNA lowered the threshold for the Ca(2+)-induced current response, mimicking the enhancement of current activation exerted by anti-annexin IV antibody. The inhibitory effect of annexin IV on Ca(2+)-dependent Cl- conductance represents a novel mechanism by which Ca(2+)-binding proteins modulate membrane channel activity.
Kaetzel
M A
MA
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0576.
Chan
H C
HC
Dubinsky
W P
WP
Dedman
J R
JR
Nelson
D J
DJ
D000818:Animals; D017314:Annexin A4 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000378:metabolism
D017314:Annexin A4; D018118:Chloride Channels; D002712:Chlorides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000001:Calcimycin; D002118:Calcium