Inactivation of calcium-activated chloride channels in smooth muscle by calcium/calmodulin-dependent protein kinase

摘要

To determine the mechanisms responsible for the termination of Ca~2+-activated Cl~- currents (I_Cl(Ca)), simultaneous measurements of whole cell currents and intra- cellular Ca~2+ concentration ([Ca~2+]_i) were made in equine tracheal myocytes. In nondialyzed cells, or cells dialyzed with 1 mM ATP, I_Cl(Ca) decayed before the [Ca~2+]_i decline, whereas the calcium-activated potassium current decayed at the same rate as [Ca~2+]_i. Substitution of AMP-PNP or ADP for ATP markedly prolonged the decay of I_Cl(Ca), resulting in a rate of current decay similar to that of the fall in [Ca~2+]_i. In the presence of ATP, dialysis of the calmodulin antagonist W7, the Ca~2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN93, or a CaMKII-specific peptide inhibitor the rate of I_Cl(Ca) decay was slowed and matched the [Ca~2+]_i decline, whereas H7, a nonspecific kinase inhibitor with low affinity for CaMKII, was without effect.