Identification of a cardiac sodium channel insensitive to synthetic modulators.
J Cardiovasc Pharmacol Ther
; 6(2): 201-12, 2001 Apr.
Article
in En
| MEDLINE
| ID: mdl-11509927
ABSTRACT
BACKGROUND:
DPI 201-106 (DPI) was the first synthetic compound showing cardioselective modulation of voltage-gated sodium channels (VGSCs) resulting in a positive inotropic effect. Currently, the exact mode of action for this class of compounds is not known.METHODS:
Effects of different natural and synthetic sodium channel modulators were investigated in cardiac tissue of several species with conventional electrophysiologic methods.RESULTS:
In electrically driven cardiac tissues, all compounds investigated increased force of contraction (FC) and action potential duration (APD) with increasing concentrations except for DPI in cattle trabecular muscle, which demonstrated no effect. Interestingly, calculation of EC50 levels at 30% repolarization demonstrates that natural VGSC-ligands were highly potent in prolonging the APD in cattle whereas no positive trends could be obtained for DPI and SDZ 211-939 (SDZ) in cattle.CONCLUSIONS:
These results demonstrate that the binding site for DPI and SDZ is distinct from sites 2 or 3 of the VGSC alpha-subunit. Moreover, this is the first time that these compounds show no effect or even shortening of APD. This finding will enable the characterization of the mode of action and probably the binding site for synthetic VGSC-modulators.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sodium Channels
/
Myocardium
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Cardiovasc Pharmacol Ther
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
FARMACOLOGIA
Year:
2001
Document type:
Article
Affiliation country:
Switzerland