PMID- 10218481
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 448
IP  - 2-3
DP  - 1999 Apr 9
TI  - Functional consequences of a domain 1/S6 segment sodium channel mutation
      associated with painful congenital myotonia.
PG  - 231-4
AB  - An unusual form of painful congenital myotonia is associated with a novel SCN4A
      mutation causing a valine to methionine substitution in the domain 1/S6 segment
      of the skeletal muscle sodium channel. We studied the functional characteristics 
      of this mutant allele using a recombinant channel to gain understanding about the
      nature of the biophysical defect responsible for this unique phenotype. When
      expressed heterologously in a cultured mammalian cell line (tsA201), the mutant
      channel exhibits subtle defects in its gating properties similar, but not
      identical, to other myotonia-producing sodium channel mutations. The main
      abnormalities are the presence of a small non-inactivating current that occurs
      during short test depolarizations, a shift in the voltage-dependence of channel
      activation to more negative potentials, and a slowing of the time course of
      recovery from inactivation. Flecainide, a potent sodium channel blocker
      previously reported to benefit patients affected by this form of myotonia,
      effectively inhibits the abnormal sodium current associated with expression of
      the mutant channel. Our findings demonstrate the unique pattern of sodium channel
      dysfunction associated with a D1/S6 myotonia-producing sodium channel mutation,
      and provide a mechanism for the beneficial effects of flecainide in this setting.
FAU - Wang, D W
AU  - Wang DW
AD  - Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN
      37232, USA.
FAU - VanDeCarr, D
AU  - VanDeCarr D
FAU - Ruben, P C
AU  - Ruben PC
FAU - George, A L Jr
AU  - George AL Jr
FAU - Bennett, P B
AU  - Bennett PB
LA  - eng
GR  - HL51197/HL/NHLBI NIH HHS/United States
GR  - NS32387/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Sodium Channels)
RN  - K94FTS1806 (Flecainide)
SB  - IM
MH  - Animals
MH  - Anti-Arrhythmia Agents
MH  - Cell Line
MH  - Computer Simulation
MH  - Flecainide/pharmacology
MH  - Ion Channel Gating
MH  - Membrane Potentials
MH  - Muscle, Skeletal/physiology
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Myotonia Congenita/*genetics
MH  - Sodium Channels/*genetics
MH  - Time Factors
EDAT- 1999/04/28 02:03
MHDA- 2001/03/28 10:01
CRDT- 1999/04/28 02:03
PHST- 1999/04/28 02:03 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/04/28 02:03 [entrez]
AID - S0014-5793(99)00338-5 [pii]
AID - 10.1016/s0014-5793(99)00338-5 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Apr 9;448(2-3):231-4. doi: 10.1016/s0014-5793(99)00338-5.