1. Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes
- Author
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Bo-Wei Wu, Dong-mei Wu, and Xiong Wang
- Subjects
Male ,medicine.medical_specialty ,Adenosine ,Cardiotonic Agents ,Indoles ,Calcium Channels, L-Type ,Pyridines ,Heart Ventricles ,Cell Separation ,Adenosine A1 Receptor Antagonists ,Biology ,Maleimides ,Adenosine A1 receptor ,Basal (phylogenetics) ,Internal medicine ,medicine ,Animals ,Myocytes, Cardiac ,Pharmacology (medical) ,L-type calcium channel ,Patch clamp ,Rats, Wistar ,Receptor ,Protein Kinase C ,Protein kinase C ,Pharmacology ,Dose-Response Relationship, Drug ,Voltage-dependent calcium channel ,Imidazoles ,General Medicine ,Rats ,Endocrinology ,Xanthines ,medicine.drug - Abstract
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: I Ca-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 mumol/L). PD116948 (30 mumol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I Ca-L . However, GF109203X (0.4 mumol/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 ICa-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 ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal I Ca-L at downstream-mechanism.
- Published
- 2005