What is the clinical evidence from this study?

Study design: Observational. Population: Brugada syndrome (n=6). Intervention: SCN5A gene mutations vs. Wild-type sodium channel proteins. Primary outcome: Cardiac sodium channel characteristics (steady-state activation and inactivation curves).

What question did this study set out to answer?

To explore how mutations in the SCN5A gene alter cardiac sodium channel function associated with Brugada syndrome.

December 1, 1999Cardiovascular ResearchOpen Access

Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome

View Full Paper

Ask AI

Bookmark

Key result

SCN5A missense mutations (R1512W and A1924T) associated with Brugada syndrome significantly alter cardiac sodium channel kinetics, causing a 4-9 mV negative voltage shift in steady-state activation.

Population

6 affected individuals with Brugada syndrome and Xenopus oocytes expressing wild-type and mutant sodium…

Comparison

Expression of mutant SCN5A sodium channel proteins vs Expression of wild-type SCN5A sodium channel…

Design

Preclinical

Authors

MRMieneke RookMartini Ziekenhuis

Discussion

Member takes

Implication

Informs mechanistic studies of Brugada syndrome; leaves open clinical translation from animal data.

Key Points

To explore how mutations in the SCN5A gene alter cardiac sodium channel function associated with Brugada syndrome.
Used a candidate gene approach focusing on SCN5A in six individuals with Brugada syndrome.
Identified missense mutations (R1512W, A1924T) and analyzed their impact on channel kinetics using Xenopus oocyte expression.
Examined the voltage shifts in activation and inactivation curves of sodium channels due to mutations.
The R1512W mutation caused a 4-5 mV negative shift in steady-state activation and inactivation curves.
The A1924T mutation resulted in a 9 mV negative shift in the steady-state activation curve.
Both mutations were linked to increased inward sodium current during action potential upstroke.

Study Design

Type

Observational (n=6)

Structured PICO

Population

6 patients with Brugada syndrome evaluated for SCN5A mutations and their functional consequences.

Exposure

Expression of mutant SCN5A sodium channel proteins (R1512W and A1924T)

Comparator

Expression of wild-type SCN5A sodium channel proteins

Outcome

Functional consequences on cardiac sodium channel characteristics (steady-state activation and inactivation curves, recovery from inactivation, time-dependent kinetics)surrogate

SCN5A mutations associated with Brugada syndrome significantly alter cardiac sodium channel kinetics, likely increasing inward sodium current during the action potential upstroke.

Cite This Study

Mieneke Rook (1999) conducted an observational in Brugada syndrome (n=6). SCN5A gene mutations vs. Wild-type sodium channel proteins was evaluated on Cardiac sodium channel characteristics (steady-state activation and inactivation curves). SCN5A missense mutations (R1512W and A1924T) associated with Brugada syndrome significantly alter cardiac sodium channel kinetics, causing a 4-9 mV negative voltage shift in steady-state activation.

synapsesocial.com/papers/6a2038adeab213b7bb295762 https://doi.org/10.1016/s0008-6363(99)00350-8

View Full Paper

Ask AI

Bookmark

Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Also Consider

Also Consider