Ca2+ influx through nonselective cation channels plays an essential role in noradrenaline-induced arachidonic acid release in Chinese hamster ovary cells expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors

We constructed Chinese hamster ovary (CHO) cells stably expressing alpha (1 A)-, alpha (1B)-, or alpha (1D)-adrenergic receptors (CHO-alpha (1A), CHO-a lpha (1B), or CHO-alpha (1D), respectively) and compared the Ca2+ channels activated by noradrenaline (NA) in these cells using whole-cell recordings and monitoring of the intracellular free Ca2+ concentration ([Ca2+](i)). We also investigated the involvement of Ca2+ channels in the NA-Induced arach idonic acid release. In all three cell types, NA at concentrations greater than or equal to 10 nM induced a sustained increase in [Ca2+](i) attributab le to extracellular Ca2+ influx in [Ca2+](i) monitoring and an inward curre nt in whole-cell recording. The current-voltage relationships were linear, and their reversal potentials were close to 0 mV. The reversal potential of the currents was not affected by a change in the concentration of Cl- in t he bath solution. Moreover, a current could be induced in a bath solution c ontaining only Ca2+ as the movable cation. LOE 908, a receptor-operated Ca2 + channel blocker, inhibited the sustained increase in [Ca2+](i) and inward currents in a concentration-dependent manner, and complete inhibition was observed at concentrations greater than or equal to3 muM. NA induced arachi donic acid release in all three cell types. This release was entirely depen dent on extracellular Ca2+ influx. Moreover, LOE 908 at concentrations grea ter than or equal to3 muM blocked the NA-induced increase in arachidonic ac id release. These results indicate that 1) NA activates LOE 908-sensitive C a2+-permeable nonselective cation channels (NSCCs) in CHO-alpha (1A), CHO-a lpha (1B), and CHO-alpha (1D), and 2) the Ca2+ influx through NSCCs may pla y an important role in the NA-induced enhancement of arachidonic acid relea se in these cells.