Open chain crown-type polyethers and pyridinophane cryptands act as ionophores upon frog motor nerve and isolated rat heart cells.
Frog motor nerves and isolated heart cells from neonatal rats were incubated with solutions of open chain crown-type polyether or pyridinophane cryptand. The following alterations in membrane excitability and energy consumption were found: 1. The non-cyclic ligand stabilizes the resting potential of the frog nerve and reduces the pulsation rate of heart muscle cells. It is reversibly bound at the cell surface and does not affect the energy metabolism of the heart cells. (formula: see text) 2. The cryptand 1,12-dioxo-2,11-diaza-5,8,21,24-tetraoxa[12-8(2,11)] (2,6)-pyridinophane) ([2.2.1py]-diamide) is irreversibly bound by the tissues. It facilitates the depolarization of the nerve and shows a positively chronotropic effect upon the heart muscle cells. Single treatment of the cell cultures with 10 microgram [2.2.1py]-diamide per ml medium increased the activities of lactate dehydrogenase and of creatine kinase. When the cell cultures were treated three times at 24 h intervals with 10 microgram complexone/ml, the creatine kinase activity of the heart muscle cells decreased by about 40%. The physiological properties of the ligands are correlated with the stability of their alkali metal ion complexes and with the rate constants of complex formation. It is concluded that [2.2.1py]-diamide can act as a passive carrier for Na+ K+.
D000818:Animals; D001001:Anura; D004734:Energy Metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011893:Rana esculenta; D011896:Rana temporaria; D051381:Rats; D013329:Structure-Activity Relationship
D004988:Ethers, Cyclic; D007476:Ionophores; D011725:Pyridines; D011804:Quinolines; C016706:pyridinophane cryptand