Acta Pharmacologica Sinica 2005 May; 26 (5): 559-562; doi: 10.1111/j.1745-7254.2005.00107.x

Aim: To compare the effects of AMP579 and adenosine on L-type Ca²⁺ current (I_Ca-L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on I_Ca-L.

Methods:  I_Ca-L was recorded by patch-clamp technique in whole-cell configuration.

Results: Adenosine (10 nmol/L to 50 µmol/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 IC₅₀ of 13.06 µmol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I_Ca-L induced by isoproterenol. AMP579 and adenosine (both in 10 µmol/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 IC₅₀ (1.17 µmol/L). PD116948 (30 µmol/L), an adenosine A₁ 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 A₁ 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.

Keywords: AMP579; adenosine; heart ventricles; cardiac myocytes; L-type calcium channels; patch-clamp techniques