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

• Main Authors: Meimi Zhao (Author), Rui Feng (Author), Dongxue Shao (Author), Shuyuan Liu (Author), Ming Lei (Author), Hongmei Wang (Author), Xuefei Sun (Author), Feng Guo (Author), Huiyuan Hu (Author), Masaki Kameyama (Author), Liying Hao (Author)
• Format: Book
• Published: Elsevier, 2015-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1347-8613; 10.1016/j.jphs.2015.08.001
• Keywords: Mg2+; Ca2+ channels; Open probability; Open time; Inside-out configuration; Therapeutics. Pharmacology; RM1-950
• Source: Journal of Pharmacological Sciences, Vol 129, Iss 3, Pp 143-149 (2015)

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.