Effect of manganese (II) bis(glycinate)dichloride on Ca2+ channel function in cultured chick atrial cells

Abstract Manganese (II) bis(glycinate)dichloride (Mn(glycinate) 2 ) is a coordination complex of manganese with application as a contrast enhancement agent for magnetic resonance imaging in the heart. To determine the cardioactivity of the manganese ion in this chelation cage, the effects of Mn(glycinate) 2 on Ca channel function in the cultured chick atrial cell was studied. Mn(glycinate) 2 decreased amplitude of contraction in chick atrial cells from embryos 14 days in ovo with complete inhibition of beating at 1 mM and half-maximal effect at 0.1 mM. Under control conditions, Bay K 8644, a Ca channel activator increased amplitude of contraction by 86% with a half maximal effect at 3.2 × 10 −7 M. In the presence of 0.025 mM Mn(glycinate) 2 , a concentration which had no effect on the amplitude of contraction, the maximum response to Bay K 8644 was decreased to 31%. Mn(glycinate) 2 had no effect on the EC 50 for the response to Bay K 8644, 1.7 ± 0.1 × 10 −9 M (S.E.M., n = 4) in control cells compared to 2.2 ± 0.4 × 10 −9 M(S.E.M., n = 4) in cells incubated with Mn(glycinate) 2 . 45 Ca 2+ uptake over 5 min in cultured chick atrial cells decreased from 2.0 nmol/mg protein in control cells to 1.5 nmol/mg protein in the presence of 10 −5 M PN200-110, a Ca 2+ channel blocker, a decrease of 28%. 45 Ca 2+ uptake decreased to 0.94 nmol/mg protein (53%) in the presence of 1 nmol Mn(glycinate) 2 . Effects of Mn(glycinate) 2 and PN200 were not additive. These data demonstrate that Mn(glycinate) 2 exerts its negative inotropic effect, at least partially, by interfering with the function of the L-type Ca channels at high concentrations.