Cyclopiazonic acid activates a Ca2+-permeable, nonselective cation conductance in porcine and bovine tracheal smooth muscle

Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Ontario, Canada Submitted 1 March 2005 ; accepted in final form 7 July 2005 Capacitative Ca 2+ entry has been examined in several tissues and, in some, appears to be mediated by nonselective cation channels collectively referred to as "store-operated" cation channels; however, relatively little is known about the electrophysiological properties of these channels in airway smooth muscle. Consequently we examined the electrophysiological characteristics and changes in intracellular Ca 2+ concentration associated with a cyclopiazonic acid (CPA)-evoked current in porcine and bovine airway smooth muscle using patch-clamp and Ca 2+ -fluorescence techniques. In bovine tracheal myocytes, CPA induced an elevation of intracellular Ca 2+ that was dependent on extracellular Ca 2+ and was insensitive to nifedipine (an L -type voltage-gated Ca 2+ channel inhibitor). Using patch-clamp techniques and conditions that block both K + and Cl – currents, we found that CPA rapidly activated a membrane conductance ( I CPA ) in porcine and bovine tracheal myocytes that exhibits a linear current-voltage relationship with a reversal potential around 0 mV. Replacement of extracellular Na + resulted in a marked reduction of I CPA at physiological membrane potentials (i.e., –60 mV) that was accompanied by a shift in the reversal potential for I CPA toward more negative membrane potentials. In addition, I CPA was markedly inhibited by 10 µM Gd 3+ and La 3+ but was largely insensitive to 1 µM nifedipine. We conclude that CPA induces capacitative Ca 2+ entry in porcine and bovine tracheal smooth muscle via a Gd 3+ - and La 3+ -sensitive, nonselective cation conductance. sarcoplasmic reticulum Ca 2+ -ATPase; nonselective cation channel; voltage-gated Ca 2+ channels; capacitative Ca 2+ entry Address for reprint requests and other correspondence: L. J. Janssen, St. Joseph's Hospital, Rm. L314, 50 Charlton Ave. East, Hamilton, Ontario, Canada, L8N 4A6 (e-mail: janssenl{at}mcmaster.ca )