The sodium channel  -subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart

2001 ◽  
Vol 537 (3) ◽  
pp. 693-700 ◽  
Author(s):  
A. I Fahmi ◽  
M. Patel ◽  
E. B Stevens ◽  
A. L Fowden ◽  
J. E. John ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Kinetics Of

scholarly journals Detection of Paralytic Shellfish Poison by Rapid Cell Bioassay: Antagonism of Voltage-Gated Sodium Channel Active Toxins in vitro

2003 ◽  
Vol 86 (3) ◽  
pp. 540-543 ◽  
Author(s):  
Ronald L Manger ◽  
Linda S Leja ◽  
Sue Y Lee ◽  
James M Hungerford ◽  
Mary Ann Kirkpatrick ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Mouse Bioassay ◽  
Marine Toxins ◽  
Prolonged Incubation ◽  
Paralytic Shellfish Poison ◽  
Paralytic Shellfish ◽  
Channel Blocking ◽  
In Vitro Effects ◽  
Kinetics Of

Abstract Although cytotoxicity assays provide several advantages over mouse bioassays, sodium channel-blocking marine toxins, such as those associated with paralytic shellfish poison (PSP), require prolonged incubation periods of 24–48 h. This is in marked contrast to in vitro detection of sodium channel-enhancing marine toxins such as ciguatoxins or brevetoxins which can be accomplished in as few as 4–6 h. We developed a modified PSP cell bioassay that is as rapid as in vitro methods for sodium channel-enhancing toxins. The cell bioassay is based on a saxitoxin-dependent antagonism of the rapid in vitro effects of brevetoxin or ciguatoxin. Comparative analysis of naturally incurred PSP residues by both antagonism cell bioassay and the mouse bioassay demonstrated significant correlation. The simplicity, sensitivity, and enhanced kinetics of the new antagonism cell bioassay format provide the basis for development of a practical alternative to conventional mouse testing for PSP.

scholarly journals Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating.

1996 ◽  
Vol 107 (2) ◽  
pp. 183-194 ◽  
Author(s):  
S Ji ◽  
A L George ◽  
R Horn ◽  
R L Barchi
Keyword(s):  
Steady State ◽  
Sodium Channel ◽  
Molecular Mechanisms ◽  
Dominant Role ◽  
Channel Gating ◽  
Paramyotonia Congenita ◽  
Double Mutation ◽  
Recovery From Inactivation ◽  
Steady State Inactivation ◽  
Kinetics Of

Mutations in the gene encoding the voltage-gated sodium channel of skeletal muscle (SkMl) have been identified in a group of autosomal dominant diseases, characterized by abnormalities of the sarcolemmal excitability, that include paramyotonia congenita (PC) and hyperkalemic periodic paralysis (HYPP). We previously reported that PC mutations cause in common a slowing of inactivation in the human SkMl sodium channel. In this investigation, we examined the molecular mechanisms responsible for the effects of L1433R, located in D4/S3, on channel gating by creating a series of additional mutations at the 1433 site. Unlike the R1448C mutation, found in D4/S4, which produces its effects largely due to the loss of the positive charge, change of the hydropathy of the side chain rather than charge is the primary factor mediating the effects of L1433R. These two mutations also differ in their effects on recovery from inactivation, conditioned inactivation, and steady state inactivation of the hSkMl channels. We constructed a double mutation containing both L1433R and R1448C. The double mutation closely resembled R1448C with respect to alterations in the kinetics of inactivation during depolarization and voltage dependence, but was indistinguishable from L1433R in the kinetics of recovery from inactivation and steady state inactivation. No additive effects were seen, suggesting that these two segments interact during gating. In addition, we found that these mutations have different effects on the delay of recovery from inactivation and the kinetics of the tail currents, raising a question whether this delay is a reflection of the deactivation process. These results suggest that the S3 and S4 segments play distinct roles in different processes of hSkM1 channel gating: D4/S4 is critical for the deactivation and inactivation of the open channel while D4/S3 has a dominant role in the recovery of inactivated channels. However, these two segments interact during the entry to, and exit from, inactivation states.

Abstract 17032: Substrate Stiffness Alters the Kinetics of Sodium Channel Nav1.5 and Depolarization of Cardiomyocytes

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Yutao T Xi ◽  
Sheng-An T Su ◽  
Luiz C Sampaio ◽  
Shui Ping T So ◽  
Junping T Sun ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Substrate Stiffness ◽  
Inactivation Curve ◽  
Hek 293 ◽  
Cell Substrate ◽  
Rat Hearts ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Reentrant Arrhythmia ◽  
Kinetics Of

Background: Myocardial scarring after infarction (MI) can create areas of slowed conduction, which can lead to re-excitation of the heart, or re-entry. Reentrant arrhythmia is one of the electrophysiological mechanisms responsible for ventricular tachycardia after acute myocardial infarction (AMI). Since the sodium channel (Na v 1.5) is a major contributor to cardiac electrical conduction, the objective of this study was to evaluate the effect of cell substrate stiffness on the kinetics of the Na v 1.5. Methods: MI was created by permanent ligation of the left anterior descending artery in rats. After 7 days, hearts were decellularized and grossed into 1 mm rings for measuring stiffness by using an atomic force microscope. The hearts had an elastic modulus of 263.33±76.8 kPa at scar, and 27.26±3.97 kPa at a remote area (n=3). The surface of p olydimethylsiloxane (PDMS) gels was tuned to match the stiffness of decellularized infarcted rat hearts (17.04±2.02 kPa, 110.56±8.70 kPa and 328.4±45.72 kPa, respectively, n=3). Human embryonic kidney 293 (HEK-293) cells were induced to stably express human Na v 1.5. HEK-293 and human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were separately cultured on the PDMS substrate that mimicked stiffness of infarcted rat hearts for 24 h. Sodium channel currents (I Na ) and action potentials (APs) were recorded by patch clamp techniques. Results: As substrate stiffness increased, HEK-293 voltage dependent activation of Na v 1.5 (I Na ) shifted significantly towards more positive voltage (Vhalf: -28.42±5.12 mV, -33.47±6.98 mV, -19.84±5.24 mV, respectively, p<0.01 in one-way ANOVA, n=12), and the transition from closed-state into inactivation was faster (tau: 48.47±4.60ms, 40.67±8.07ms, 81.20±9.54ms, p<0.05, n=12). However, the current density, the steady-state inactivation curve and the recovery time were comparable between different PDMS. In iPSC-CMs, the slope of AP upstroke was decreased when stiffness was increased (30.00±1.38V/s, 23.91±0.65V/s, 20.93±0.34V/s, p<0.05, n=15). Conclusion: Increased substrate stiffness, similar to myocardial scar, alters the kinetics of Na v 1.5 and affects the depolarization of cardiomyocytes, which likely contributes to slow conduction after MI.

Kinetics of interaction of disopyramide with the cardiac sodium channel: Fast dissociation from open channels at normal rest potentials

1993 ◽  
Vol 136 (2) ◽  
pp. 199-214 ◽  
Author(s):  
Augustus O. Grant ◽  
David J. Wendt ◽  
Yuri Zilberter ◽  
C. Frank Starmer
Keyword(s):  
Sodium Channel ◽  
Open Channels ◽  
Cardiac Sodium Channel ◽  
Kinetics Of

scholarly journals Kinetic Analysis of Block of Open Sodium Channels by a Peptide Containing the Isoleucine, Phenylalanine, and Methionine (IFM) Motif from the Inactivation Gate

1998 ◽  
Vol 111 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Galen Eaholtz ◽  
William N. Zagotta ◽  
William A. Catterall
Keyword(s):  
Electric Field ◽  
Sodium Channel ◽  
Kinetic Analysis ◽  
Sodium Channels ◽  
Rate Constant ◽  
Voltage Dependence ◽  
Bimolecular Reaction ◽  
Voltage Dependent ◽  
Kinetics Of ◽  
The Brain

We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was ∼33 μM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of ∼0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

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