Carol Ann

Cincinnati CityBeat 811 Race Street, 4th Floor Cincinnati, OH 45202

republicanherald.com 111 Mahantongo St. Pottsville, PA 17901 Phone: 570-622-3456 Email: [email protected]

republicanherald.com 111 Mahantongo St. Pottsville, PA 17901 Phone: 570-622-3456 Email: [email protected]

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republicanherald.com 23 S. Centre St.,2nd Floor Pottsville, PA 17901 Phone: 570-622-3456 Email: [email protected]

Local Obituaries Each day's obituaries, delivered to your inbox.

A comprehensive approach to evaluate genetic abnormalities in multiple myeloma using optical genome mapping ...

A sodium current (INa) reduction occurs in the setting of many acquired and inherited conditions and is associated with cardiac conduction slowing and increased arrhythmia risks. The sodium channel blocker mexiletine has been shown to restore the trafficking of mutant sodium channels to the membrane. However, these studies were mostly performed in heterologous expression systems using high mexiletine concentrations. Moreover, the chronic effects on INa in a non-diseased cardiomyocyte environment remain unknown. In this paper, we investigated the chronic and acute effects of a therapeutic dose of mexiletine on INa and the action potential (AP) characteristics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of a healthy individual. Control hiPSC-CMs were incubated for 48 h with 10 µM mexiletine or vehicle. Following the wash-out of mexiletine, patch clamp analysis and immunocytochemistry experiments were performed. The incubation of hiPSC-CMs for 48 h with mexiletine (followed by wash-out) induced a significant increase in peak INa of ~75%, without any significant change in the voltage dependence of (in)activation. This was accompanied by a significant increase in AP upstroke velocity, without changes in other AP parameters. The immunocytochemistry experiments showed a significant increase in membrane Nav1.5 fluorescence following a 48 h incubation with mexiletine. The acute re-exposure of hiPSC-CMs to 10 µM mexiletine resulted in a small but significant increase in AP duration, without changes in AP upstroke velocity, peak INa density, or the INa voltage dependence of (in)activation. Importantly, the increase in the peak INa density and resulting AP upstroke velocity induced by chronic mexiletine incubation was not counteracted by the acute re-administration of the drug. In conclusion, the chronic administration of a clinically relevant concentration of mexiletine increases INa density in non-diseased hiPSC-CMs, likely by enhancing the membrane trafficking of sodium channels. Our findings identify mexiletine as a potential therapeutic strategy to enhance and/or restore INa and cardiac conduction.

When I find myself hugging the turns on Jekyll Island's north end, I'm usually heading one of two places. It's either for a walk along the secluded shores of Driftwood Beach or to a date night dinner at Driftwood Bistro (which offers a vegan-vegetarian menu, God bless them).