T-type and L-type Ca2+ currents in canine bronchial smooth muscle: characterization and physiological roles

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Abstract
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 1) exhibited threshold and peak activation at approximately -35 mV and +10 mV, respectively; 2) inactivated slowly with half-inactivation at -20 mV; 3) deactivated rapidly (time constant < 1 ms) upon repolarization; and 4) was abolished by nifedipine and suppressed by cholinergic agonist. These characteristics are typical of L-type Ca2+ current. During depolarization from -70 or -80 mV, however, many cells exhibited 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 10 ms). Inactivation of the other current was also rapid (time constant approximately 3 ms) and half-maximal at approximately -70 mV. There was a persistent “window” current over the physiologically relevant range 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 upon repolarization to the holding potential decayed approximately 10 times more slowly than did L-type tail currents. These characteristics are all typical of T-type Ca2+ current. We conclude that there is a prominent T-type Ca2+ current in canine bronchial smooth muscle; this current may play a central role in excitation-contraction coupling, in refilling of the internal Ca2+ pool, and in electrical slow waves. Because airflow resistance is determined primarily by the smaller airways and not the trachea, these findings may have important implications with respect to airway physiology and the mechanisms underlying airway hyperreactivity and asthma.