Modulation of Nav1.5 by ?1- and ?3-subunit co-expression in mammalian cells

Autor: Paul W. Lenkowski, J. Paul Mounsey, Seong Hoon Ko, Manoj K. Patel, Hwa C. Lee
Rok vydání: 2004
Předmět:
Zdroj: Pfl�gers Archiv - European Journal of Physiology. 449:403-412
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-004-1348-4
Popis: Cardiac sodium channels (Nav1.5) comprise a pore-forming α-subunit and auxiliary β-subunits that modulate channel function. In the heart, β1 is expressed throughout the atria and ventricles, whilst β3 is present only in the ventricles and Purkinje fibers. In view of this expression pattern, we determined the effects of β3 and β1 co-expression alone, and in combination, on Nav1.5 stably expressed in Chinese hamster ovary cells. The current/voltage relationship was shifted −5 mV with either β1 or β3 co-expression alone and −10 mV with co-expression of both β1 and β3. In addition, β3 and β1/β3 co-expression accelerated macroscopic current decay. There were significant hyperpolarizing shifts in equilibrium gating relationships with co-expression of β1 and β3 alone and in combination. Co-expression of β1/β3 together resulted in a greater hyperpolarizing shift in channel availability, and an increase in the slopes of equilibrium gating relationships. Co-expression of β3 and β1/β3, but not β1, slowed recovery from inactivation at −90 mV. Development of inactivation at −70 and −50 mV was accelerated by β-subunit co-expression alone and in combination. β-Subunit co-expression also reduced the late Na current measured at 200 ms. In conclusion, β-subunits modulate Nav1.5 gating with important differences between co-expression of β1 and β3 alone and β1/β3 together.
Databáze: OpenAIRE
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