Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes

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).

I(Ca-L) was recorded by patch-clamp technique in whole-cell configuration.

Adenosine (10 nmol/L to 50 micromol/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 micromol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I(Ca-L) induced by isoproterenol. AMP579 and adenosine (both in 10 micromol/L) suppressed isoproterenol-induced ICa-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 micromol/L). PD116948 (30 micromol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I(Ca-L). However, GF109203X (0.4 micromol/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.

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.