Summary
A single glass micropipette voltage clamp technique with intracellular dialysis was used to study the effects of the trapidil derivatives AR 12–456 and AR 12–463 on Ca channel currents carried by Bat+ in isolated ventricular cells from mice hearts. Inspite of a more potent inhibition of the cAMP phosphodiesterase from heart (Bartel et al. 1985) a reversible Ca channel blocking action of both compounds could be observed. The concentration of half maximal block was calculated to about 50 μmol/l for both derivatives tested. Neither a shift in the current-voltage relationships nor a significant change in the potential for half maximal activation was found. The maximal Ba2+ -conductance was reduced. The steady state inactivation was shifted towards more negative potentials by application of 100 μmol/l AR 12–463. The decay of the Ba currents was accelerated in the range of the applied test potentials between −20 and +20 mV. It is concluded that the new trapidil derivatives with more potent inhibitory action on cardiac phosphodiesterase than trapidil can block myocardial Ca channels.
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Markwardt, F., Nilius, B. Effects of trapidil-derivatives on calcium channel currents in isolated ventricular cells from mice. Naunyn-Schmiedeberg's Arch Pharmacol 337, 454–458 (1988). https://doi.org/10.1007/BF00169539
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DOI: https://doi.org/10.1007/BF00169539