NaV1.5-Late - "INa-Late recorded from CHO cells and hiPSC-CMs on Nanion´s Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.5 MB)
Cells were kindly provided by Charles River.
iCell® Cardiomyocytes2 were kindly provided by Fujifilm Cellular Dynamics International.

Summary:

The voltage-gated Na+ channel 1.5 (NaV1.5) is encoded by the SCN5A gene and is responsible for the rising phase of the cardiac action potential (AP). The NaV1.5 channel is comprised of a pore-forming α subunit and auxillary β subunits. When the cardiac cell membrane depolarizes, NaV1.5 opens for a short time allowing an influx of Na+ ions resulting in the upstroke of the AP. During the AP, these channels can recover from inactivation and re-open resulting in a sustained current termed INa-Late. Although this current is substantially smaller than the peak Na+ current (INa-Peak), it is active during the plateau phase and therefore contributes to AP morphology. There is a growing body of evidence that increased INa-Late can have a pathophysiological role in acquired heart diseases such as myocardial ischemia and heart failure. INa-Late is elevated in several pathological conditions which could result in Na+-overload in these cells. A number of loss or gain-of-function mutations in the SCN5A gene have been identified which lead to changes in the magnitude or duration of INa-Peak or INa-Late resulting in fatal arrhythmias. INa-Late is a potential drug target to treat cardiac disorders such as angina, heart failure and arrhythmia. It is also an important target in safety pharmacology as enhancement of INa-Late is proarrhythmic.

In this study the Patchliner was used to record INa-Late from CHO cells and hiPSC-CMs. INa-Late was recorded using the voltage protocol specified by CiPA and activated using ATX-II. INa-Late could be recorded from CHO cells stably expressing NaV1.5 and blocked by lidocaine. INa-Late could also be detected in iCell® Cardiomyoctes2 and blocked by ranolazine.

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