Abstract: AIM: To investigate the effects of CPU 228 on cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and the parameters of Ca²⁺ transients in myocardium during β-adrenergic stimulation.METHODS: The cytosolic Ca²⁺ concentration of the isolated rat ventricular myocytes was measured by Fluo-3/AM.The Ca²⁺ transient of myocytes was twitched by 0.5 Hz field stimulation.Isoproterenol (ISO) 100 nmol°L^-1 was used for stimulate the β-adrenoceptor. The effects of CPU 228 1 μmol°L^-1 on [Ca²⁺]_i, the intracellular Ca²⁺ load level, Ca²⁺ transient duration and decay ratio was observed.RESULTS: ISO 100 nmol°L^-1 significantly increased the [Ca²⁺]_i, intracellular Ca²⁺ load level, and the post-peak decay ratio of cytosolic Ca²⁺, but it reduced the Ca²⁺ peak duration of Ca²⁺ transients in isolated rat ventricular myocytes. CPU 228 1 μmol°L^-1 did not affect the [Ca²⁺]_i in isolated rat ventricular myocytes, but it significantly restored the ISO-induced changes of [Ca²⁺]_i and Ca²⁺ transients to control level in concentration-dependent manner.CONCLUSION: CPU 228 can inhibit the increase of [Ca²⁺]_i, and restore the changed Ca²⁺ transients to control level during β-adrenergic stimulation. These effects of CPU 228 maybe due to its blockade of β-adrenoceptor or relate to its signal pathway and inhibition of the hyperphosphorylation effects.

Key words: CPU 228, ventricular myocytes, isoproterenol, Ca²⁺ transients, Fluo-3