Background: The neurohypophyseal hormones oxytocin (OT) and [Arg8]-vasopressin (AVP) have recently been implicated in cardiac function. This study was designed to investigate actions of OT and AVP on regulation of the voltage-gated Ca2+ channel in cardiomyocytes. Methods and Results: Cultured neonatal rat cardiomyocytes were stimulated with OT or AVP (10-8 M to 10-6 M) for 24-72 h, followed by real-time PCR and patch clamp studies. Although OT did not exert any modulatory effect on L-type Ca2+ channel current, as a shortterm effect, stimulation of cardiomyocytes with OT but not AVP decreased the expression of Cav1.2 mRNA with a reduced L-type Ca2+ channel current. A transcription factor CREB mRNA expression was down-regulated by OT treatment, although T-type Ca2+ channels (Cav3.1, Cav3.2) were unaffected by OT or AVP. Conclusion: OT but not AVP down-regulates L-type Ca2+ channel expression through the inhibition of CREB transcriptional, suggesting a novel mechanism of OT action in the cardiac electrophysiology.