Key result
9-phenanthrol suppressed transient outward, rapid delayed rectifier, and inward rectifier K+ currents without affecting Ca2+ currents, indicating it is not selective for TRPM4 channels in native canine cardiac cells.
9-phenanthrol lacks selectivity for TRPM4 channels in native canine ventricular myocardium, indicating it should only be used as a TRPM4 blocker in expression systems.
Questions selectivity of 9-phenanthrol for TRPM4 in ventricular myocytes; leaves open need for more specific tools in cardiac ion channel research.
The role of transient receptor potential melastatin 4 (TRPM4) channels has been frequently tested using their inhibitor 9-phenanthrol in various cardiac preparations; however, the selectivity of the compound is uncertain. Therefore, in the present study, the concentration-dependent effects of 9-phenanthrol on major ionic currents were studied in canine isolated ventricular cells using whole-cell configuration of the patch-clamp technique and 10 mM BAPTA-containing pipette solution to prevent the Ca 2+ -dependent activation of TRPM4 channels. Transient outward (I to1 ), rapid delayed rectifier (I Kr ), and inward rectifier (I K1 ) K + currents were suppressed by 10 and 30 μM 9-phenanthrol with the blocking potency for I K1 < I Kr < I to1 and partial reversibility. L-type Ca 2+ current was not affected up to the concentration of 30 μM. In addition, a steady outward current was detected at voltages positive to –40 mV in 9-phenanthrol, which was larger at more positive voltages and larger 9-phenanthrol concentrations. Action potentials were recorded using microelectrodes. Maximal rate of depolarization, phase-1 repolarization, and terminal repolarization were decreased and the plateau potential was depressed by 9-phenanthrol (3–30 μM), congruently with the observed alterations of ionic currents. Significant action potential prolongation was observed by 9-phenanthrol in the majority of the studied cells, but only at 30 μM concentration. In conclusion, 9-phenanthrol is not selective to TRPM4 channels in canine ventricular myocardium; therefore, its application as a TRPM4 blocker can be appropriate only in expression systems but not in native cardiac cells.
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Veress et al. (2018) studied None (Healthy canine ventricular myocytes). 9-phenanthrol vs. Baseline (drug-free solution) was evaluated on Inhibition of major cardiac ionic currents (Ito1, IKr, IK1, ICa). 9-phenanthrol suppressed transient outward, rapid delayed rectifier, and inward rectifier K+ currents without affecting Ca2+ currents, indicating it is not selective for TRPM4 channels in native canine cardiac cells.
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