Abstract
Oxcytocin (OXT) and [Arg8]-vasopressin (AVP), neurohypophyseal hormones, have recently been implicated in cell growth, differentiation, and contraction in the heart. However, effects of these hormones on cardiomyocytes by means of ion channel expression and contraction modulation have not completely elucidated. This study was designed to investigate the effect of OXT and AVP on transcriptional regulation of L-type Ca2+ channel expression and cardiac contractility using neonatal rat ventricular cardiomyocytes. Cultured neonatal rat cardiomyocytes were stimulated with or without 0.01-1 μM OXT or AVP for 24-72 h. Expression of Ca2+ channel isoforms (Cav1.2, Cav1.3) and cardiac transcriptional factors (Csx/Nkx2.5, CREB, and NFATc4) was assessed by real-time PCR, while Ca2+ channel currents were measured with the patch clamp technique. Stimulation with OXT but not AVP decreased the expression of cardiomyocyte Cav1.2 mRNA in a dose- and a time-dependent manner with a reduction of L-type Ca2+ channel current. In addition, these three transcriptional factors were also down-regulated by OXT stimulation for 24-48 h. In conclusion, we found that OXT may play a role in modulation of intracellular Ca2+ homeostasis through a down-regulation of the L-type Ca2+ channel at the gene transcriptional level in cardiomyocytes. [J Physiol Sci. 2008;58 Suppl:S176]
