Properties of a store-operated nonselective cation channel in airway smooth muscle.
Passive depletion of internal Ca(2+) stores in airway smooth muscle (ASM) activates nonselective cation channels (NSCCs) that mediate capacitative Ca(2+) entry. However, the single channel properties of these cation channels have yet to be resolved and their regulation by cytosolic Ca(2+) levels ([Ca(2+)](i)) still remains unclear. NSCC currents and changes in [Ca(2+)](i) during passive depletion of internal Ca(2+) stores were monitored in isolated bovine tracheal myocytes. Loading cells with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetyl methyl ester (BAPTA-AM) to reduce [Ca(2+)](i) and thereby deplete the store augmented a basal Gd(3+)- and La(3+)-sensitive, Ca(2+)-permeable NSCC current. This current mimics that which is evoked by store depletion using the sarcoplasmic reticulum Ca(2+) pump inhibitor cyclopiazonic acid (which concurrently and transiently elevates [Ca(2+)](i)). Both interventions activated an approximately 25-pS NSCC with properties identical to both spontaneous (basal) and BAPTA-AM-evoked single channel currents. In summary, the present study provides novel evidence that a lanthanide-sensitive, 25-pS nonselective cation channel underlies both basal and store depletion-evoked membrane currents in airway smooth muscle and that this conductance likely contributes to the regulation of resting [Ca(2+)](i) and capacitative Ca(2+) entry.
Helli
P B
PB
Dept of Medicine, McMaster University, Hamilton, ON, Canada.
Janssen
L J
LJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002417:Cattle; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D028581:Lanthanoid Series Elements / Q000494:pharmacology; D008564:Membrane Potentials; D032342:Muscle Cells / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014132:Trachea / Q000378:metabolism / Q000473:pathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002412:Cations; D007211:Indoles; D007473:Ion Channels; D028581:Lanthanoid Series Elements; D014665:Vasodilator Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium; C000543:cyclopiazonic acid