Mg2+-dependent facilitation and inactivation of L-type Ca2+ channels in guinea pig ventricular myocytes

• Main Authors: Meimi Zhao, Rui Feng, Dongxue Shao, Shuyuan Liu, Ming Lei, Hongmei Wang, Xuefei Sun, Feng Guo, Huiyuan Hu, Masaki Kameyama, Liying Hao
• Format: Article
• Language: English
• Published: Elsevier 2015-11-01
• Series: Journal of Pharmacological Sciences
• Subjects: Mg2+; Ca2+ channels; Open probability; Open time; Inside-out configuration
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861315001723

This study aimed to investigate the intracellular Mg2+ regulation of the L-type Ca2+ channels in guinea pig ventricular myocytes. By adopting the inside-out configuration of the patch clamp technique, single channel currents of the L-type Ca2+ channels were recorded at different intracellular Mg2+ concentrations ([Mg2+]i). At free [Mg2+]i of 0, 10−9, 10−7, 10−5, 10−3, and 10−1 M, 1.4 μM CaM + 3 mM ATP induced channel activities of 44%, 117%, 202%, 181%, 147%, and 20% of the control activity in cell-attached mode, respectively, showing a bell-shaped concentration-response relationship. Moreover, the intracellular Mg2+ modulated the Ca2+ channel gating properties, accounting for alterations in channel activities. These results imply that Mg2+ has a dual effect on the L-type Ca2+ channels: facilitation and inhibition. Lower [Mg2+]i maintains and enhances the basal activity of Ca2+ channels, whereas higher [Mg2+]i inhibits channel activity. Taken together, our data from the application of an [Mg2+]i series suggest that the dual effect of Mg2+ upon the L-type Ca2+ channels exhibits long open-time dependence.