Results: 2

1.
Figure 2

Figure 2. From: LQTS-associated mutation A257G in ?1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype.

Localization of SNTA1 variants. Illustrated is the linear topology for SNTA1 with variant localization.

Jianding Cheng, et al. Cardiogenetics. ;1(1):136.
2.
Figure 1

Figure 1. From: LQTS-associated mutation A257G in ?1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype.

Co-transfection of SNTA1 with SCN5A. A) Representative whole-cell current traces of HEK293 cells co-expressing WT or mutant SNTA1 and SCN5A, showing increased peak INa for p.A257G-SNTA1. The currents were recorded at membrane potentials between -120 to +60 mV in 10-mV increments from a holding potential of -140 mV as depicted in the protocol inset. B) Activation was measured using this protocol: currents were elicited by step depolarization for 24 ms to different potentials between −120 mV to 60 mV from a holding potential of −140 mV. The curves were fit with a Boltzmann function where GNa = [1+exp (V1/2 - V) / K]-1, where V1/2 and k are the midpoint and slope factor, respectively. G/GNa = INa (norm)/ (V - Vrev) where Vrev is the reversal potential and V is the membrane potential. p.A257G- and p.P74L/p.A257G-SNTA1 mutations caused a statistically significant hyperpolarizing shift in steady-state activation by 2.1-2.7 mV. C) Steady-state availability from inactivation was measured using the protocol shown in the inset and was determined by fitting the data to the Boltzmann function: INa = INa-Max [1+exp (Vc - V1/2) / K]-1, where V1/2 and k are the midpoint and the slope factor, respectively, and Vc is the membrane potential. p.P74L/p.A257G-SNTA1 mutation had a statistically significant hyperpolarizing shift in steady-state inactivation by 2.6 mV. D) The peak current activation data are replotted as a conductance (G) curve with steady-state inactivation relationships to show p.A257G increases the overlap of these relationships (window current). E) The peak current activation data are replotted as a conductance (G) curve with steady-state inactivation relationships to show p.P74L/p.A257G reverses the increased overlap of these relationships. Circles indicate activation, whereas squares indicate inactivation. Lines represent fits to Boltzmann equations with parameters of the fit and n numbers in Table 1. F) shows an increase in quantified window current area for p.A257G-SNTA1 compared with both WT-SNTA1 as well as p.P74L-p.A257G-SNTA1. *P<0.05 compared with WT and p.P74L/p.A257G. The experiment numbers are shown within each bar.

Jianding Cheng, et al. Cardiogenetics. ;1(1):136.

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