Open AccessEffects of AMP579 and adenosine on L‐type Ca 2+ current in isolated rat ventricular myocytes
Author(s) -
WANG Xiong,
WU Bowei,
WU Dongmei
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00107.x
Subject(s) - adenosine , medicine , endocrinology , inhibitory postsynaptic potential , protein kinase c , adenosine receptor , chemistry , basal (medicine) , patch clamp , ic50 , myocyte , receptor , biology , in vitro , kinase , biochemistry , agonist , insulin
Aim: To compare the effects of AMP579 and adenosine on L‐type Ca 2+ current ( I Ca‐L ) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on I Ca‐L . Methods:ICa‐L was recorded by patch‐clamp technique in whole‐cell configuration. Results: Adenosine (10 nmol/L to 50 umol/L) showed no effect on basal I Ca‐L , but it inhibited the I Ca‐L induced by isoproterenol 10 nmol/L in a concentration‐dependent manner with the IC 50 of 13.06 umol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I Ca‐L induced by isoproterenol. AMP579 and adenosine (both in 10 umol/L) suppressed isoproterenol‐induced I Ca‐L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal I Ca‐L in a concentration‐dependent manner with IC 50 (1.17 μmol/L). PD116948 (30 μmol/L), an adenosine A 1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I Ca‐L . However, GF109203X (0.4 μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal I Ca‐L . So the inhibitory effect of AMP579 on basal I Ca‐L was induced through activating PKC, but not linked to adenosine A 1 receptor. Conclusion: AMP579 shows a stronger inhibitory effect than adenosine on the I Ca‐L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal I Ca‐L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal I Ca‐L at downstream‐mechanism.