Properties of a store-operated nonselective cation channel in airway smooth muscle

Passive depletion of internal Ca2+ stores in airway smooth muscle (ASM) activates nonselective cation channels (NSCCs) that mediate capacitative Ca2+ entry. However, the single channel properties of these cation channels have yet to be resolved and their regulation by cytosolic Ca2+ levels ([Ca2+] i ) still remains unclear. NSCC currents and changes in [Ca2+] i during passive depletion of internal Ca2+ 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 [Ca2+]i and thereby deplete the store augmented a basal Gd3+- and La3+-sensitive, Ca2+-permeable NSCC current. This current mimics that which is evoked by store depletion using the sarcoplasmic reticulum Ca2+ pump inhibitor cyclopiazonic acid (which concurrently and transiently elevates [Ca2+] i ). Both interventions activated an ∼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 [Ca2+] i and capacitative Ca2+ entry.