PROPERTIES OF A STORE-OPERATED NON-SELECTIVE CATION CHANNEL IN AIRWAY SMOOTH MUSCLE

¹ Dept of Medicine, McMaster University and the Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario, Canada

^* To whom correspondence should be addressed. E-mail: janssenl{at}mcmaster.ca.

	Abstract

Passive depletion of internal Ca²⁺ stores in airway smooth muscle (ASM) activates non-selective 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 calcium levels ([Ca²⁺]_i) still remains unclear. NSCC currents and changes in [Ca²⁺]_i during passive depletion of internal Ca²⁺ stores was monitored in isolated bovine tracheal myocytes. Loading cells with 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 evoked by store depletion using the sarcoplasmic reticulum Ca²⁺ pump inhibitor cyclopiazonic acid (which concurrently and transiently elevates [Ca²⁺]_i). Both interventions activated an 25pS NSCC with properties identical to both spontaneous (basal) and BAPTA-evoked single channel currents. In summary, we provide novel evidence that a lanthanide-sensitive, 25pS NSCC underlies both basal and store depletion-evoked membrane currents in ASM and that this conductance likely contributes to the regulation of resting [Ca²⁺]_i and capacitative Ca²⁺ entry.