Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells

1 The Kv4.3 gene is believed to encode a large proportion of the transient outward current (I-to), responsible for the early phase of repolarization o f the human cardiac action potential. There is evidence that this current i s involved in the dispersion of refractoriness which develops during myocar dial ischaemia and which predisposes to the development of potentially fata l ventricular tachyarrhythmias. 2 Epidemiological, clinical, animal, and cellular studies indicate that the se arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsatu rated fatty acids (n-3 PUFA) present in fsh oils. 3 We describe stable transfection of the Kv4.3 gene into a mammalian cell l ine (Chinese hamster ovary cells), and using patch clamp techniques have sh own that the resulting current closely resembles human I-to. 4 The current is rapidly activating and inactivating, with both processes b eing well fit by double exponential functions (time constants of 3.8 +/- 0. 2 and 5.3 +/- 0.4 ms for activation and 20.0 +/- 1.2 and 96.6 +/- 6.7 ms fo r inactivation at +45 mV at 23 degrees C). Activation and steady state inac tivation both show voltage dependence (V-1/2 Of activation = -6.7 +/- 2.5 m V, V-1/2 Of steady state inactivation = -51.3 +/- 0.2 mV at 23 degrees C). Current inactivation and recovery from inactivation are faster at physiolog ic temperature (37 degrees C) compared to room temperature (23 degrees C). 5 The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 o f 3.6 mu mol L-1. Blockade of the transient outward current may be an impor tant mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia.