Helli, Peter B., Evi Pertens, and Luke J. Janssen. Cyclopiazonic acid activates a Ca 2ϩ -permeable, nonselective cation conductance in porcine and bovine tracheal smooth muscle. tive Ca 2ϩ 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

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... examined the electrophysiological characteristics and changes in intracellular Ca 2ϩ concentration associated with a cyclopiazonic acid (CPA)-evoked current in porcine and bovine airway smooth muscle using patchclamp and Ca 2ϩ -fluorescence techniques. In bovine tracheal myocytes, CPA induced an elevation of intracellular Ca 2ϩ that was dependent on extracellular Ca 2ϩ and was insensitive to nifedipine (an L-type voltage-gated Ca 2ϩ channel inhibitor). Using patch-clamp techniques and conditions that block both K ϩ and Cl Ϫ currents, we found that CPA rapidly activated a membrane conductance (I CPA) in porcine and bovine tracheal myocytes that exhibits a linear currentvoltage relationship with a reversal potential around 0 mV. Replacement of extracellular Na ϩ resulted in a marked reduction of ICPA at physiological membrane potentials (i.e., Ϫ60 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 M Gd 3ϩ and La 3ϩ but was largely insensitive to 1 M nifedipine. We conclude that CPA induces capacitative Ca 2ϩ entry in porcine and bovine tracheal smooth muscle via a Gd 3ϩ -and La 3ϩsensitive, nonselective cation conductance. sarcoplasmic reticulum Ca 2ϩ -ATPase; nonselective cation channel; voltage-gated Ca 2ϩ channels; capacitative Ca 2ϩ entry