Cyclopiazonic acid activates a Ca super(2+)-permeable, nonselective cation conductance in porcine and bovine tracheal smooth muscle

Capacitative Ca super(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 super(2+) concentration associated with a cyclopiazonic acid (CPA)-evoked current in porcine and bovine airway smooth muscle using patch-clamp and Ca super(2+)-fluorescence techniques. In bovine tracheal myocytes, CPA induced an elevation of intracellular Ca super(2+) that was dependent on extracellular Ca super(2+) and was insensitive to nifedipine (an L-type voltage-gated Ca super(2+) channel inhibitor). Using patch-clamp techniques and conditions that block both K super(+) and Cl super(-) currents, we found that CPA rapidly activated a membrane conductance (I sub(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 super(+) resulted in a marked reduction of I sub(CPA) at physiological membrane potentials (i.e., -60 mV) that was accompanied by a shift in the reversal potential for I sub(CPA) toward more negative membrane potentials. In addition, I sub(CPA) was markedly inhibited by 10 mu M Gd super(3+) and La super(3+) but was largely insensitive to 1 mu M nifedipine. We conclude that CPA induces capacitative Ca super(2+) entry in porcine and bovine tracheal smooth muscle via a Gd super(3+)- and La super(3+)-sensitive, nonselective cation conductance.