Journal article
A novel Na+ channel agonist, dimethyl lithospermate B, slows Na+ current inactivation and increases action potential duration in isolated rat ventricular myocytes
British journal of pharmacology, Vol.143(6), pp.765-773
10/25/2004
DOI: 10.1038/sj.bjp.0705969
PMCID: PMC1575928
PMID: 15504759
Abstract
Voltage-gated Na
+
channel blockers have been widely used as local anaesthetics and antiarrhythmic agents. It has recently been proposed that Na
+
channel agonists can be used as inotropic agents. Here, we report the identification of a natural substance that acts as a Na
+
channel agonist.
Using the patch-clamp technique in isolated rat ventricular myocytes, we investigated the electrophysiological effects of the substances isolated from the root extract of
Salvia miltiorrhiza
, which is known as ‘Danshen' in Asian traditional medicine. By the intensive activity-guided fractionation, we identified dimethyl lithospermate B (dmLSB) as the most active component, while LSB, which is the major component of the extract, showed negligible electrophysiological effect. Action potential duration (APD
90
) was increased by 20
μ
M
dmLSB from 58.8±12.1 to 202.3±9.5 ms. In spite of the prolonged APD, no early after-depolarization (EAD) was observed.
dmLSB had no noticeable effect on K
+
or Ca
2+
currents, but selectively affected Na
+
currents (
I
Na
). dmLSB slowed the inactivation kinetics of
I
Na
by increasing the proportion of slowly inactivating component without inducing any persistent
I
Na
. The relative amplitude of slow component compared to the peak fast
I
Na
was increased dose dependently by dmLSB (EC
50
=20
μ
M
). Voltage dependence of inactivation was not affected by dmLSB, while voltage dependence of activation shifted by 5 mV to the depolarised direction.
Since the APD prolongation by dmLSB did not provoke EAD, which is thought as a possible mechanism for the proarrhythmia seen in other Na
+
channel agonists, dmLSB might be an excellent candidate for a Na
+
channel agonist.
Details
- Title: Subtitle
- A novel Na+ channel agonist, dimethyl lithospermate B, slows Na+ current inactivation and increases action potential duration in isolated rat ventricular myocytes
- Creators
- Jin-Young Yoon - New Generation University CollegeSung-Hun Ahn - Kwangshin UniversityHyuncheol Oh - Korea Research Institute of Bioscience and BiotechnologyYoung-Sup Kim - Institute of Chemical TechnologyShi Yong Ryu - Institute of Chemical TechnologyWon-Kyung Ho - New Generation University CollegeSuk-Ho Lee - Seoul National University
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.143(6), pp.765-773
- DOI
- 10.1038/sj.bjp.0705969
- PMID
- 15504759
- PMCID
- PMC1575928
- NLM abbreviation
- Br J Pharmacol
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 10/25/2004
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359824802771
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