T-TYPE AND L-TYPE CA2-MUSCLE - CHARACTERIZATION AND PHYSIOLOGICAL ROLES( CURRENTS IN CANINE BRONCHIAL SMOOTH)

We examined the voltage-dependent Ca2+ currents in freshly dissociated smooth muscle cells obtained from canine bronchi (3rd to 5th order). When cells were depolarized from -40 mV, we observed an inward current that I) exhibited threshold and peak activation at approximately -35 mV and +10 mV, respectively; 2) inactivated slowly with half-inactivat ion at -20 mV; 3) deactivated rapidly (time constant <1 ms) upon repol arization; and 4) was abolished by nifedipine and suppressed by cholin ergic agonist. These characteristics are typical of L-type Ca2+ curren t. During depolarization from -70 or -80 mV, however, many cells exhib ited a second inward current superimposed on the L-type Ca2+ current. Activation of this other current was first noted at -60 mV,was maximal at approximately -20 mV, and was very rapid (reaching a peak within 1 0 ms). Inactivation of the other current was also rapid (time constant similar to 3 ms) and half-maximal at approximately -70 mV. There was a persistent ''window'' current over the physiologically relevant rang e of potentials (i.e., -60 to -30 mV). This current was also sensitive to nifedipine (although less so than the L-type current) and to Ni2+, but not to cholinergic agonist. Finally, the tail currents evoked upo n repolarization to the holding potential decayed similar to 10 times more slowly than did L-type tail currents. These characteristics are a ll typical of T-type Ca2+ current. We conclude that there is a promine nt T-type Ca2+ current in canine bronchial smooth muscle; this current may play a central role in excitation-contraction coupling, in refill ing of the internal Ca2+ pool, and in electrical slow waves. Because a irflow resistance is determined primarily by the smaller airways and n ot the trachea, these findings may have important implications with re spect to airway physiology and the mechanisms underlying airway hyperr eactivity and asthma.