Phenylephrine (PE) induced increases in intracellular calcium ([Ca++]i) in supraoptic nucleus (SON) neurons are dependent on release of calcium from intracellular calcium stores

Activation of α1‐adrenergic receptors (α1AR) by PE induces an increase in [Ca ++ ] i in SON neurons (Song et al, AJP:Regul 291, 2006). Since α1ARs are G q/ll –coupled receptors, their activation presumably generates inositol triphosphate (IP3) resulting in release of Ca ++ from intracellular stores. However, it is also possible that PE‐induced depolarization of the membrane activates voltage gated calcium channels (VGCC) resulting in Ca++ influx. α1AR activation of protein kinase C (PKC) may also modulate ion channel activity and potentially induce Ca ++ influx independent of IP3. The current studies assessed the source of the PE stimulated increase in [Ca ++ ] i . Hypothalamo‐neurohypophyseal explants were loaded with fura‐2 AM. Changes in [Ca ++ ] i were monitored by ratiometric analysis of fluorescence excited at 340 and 380 nm. In medium containing 0.3 mM Ca ++ , PE induced increases in [Ca ++ ] i were completely suppressed when Ca ++ stores were depleted by thapsigargin. However, Ca ++ free medium eliminated the Ca ++ response to PE in ~ 2/3 of the neurons. These results indicate that PE induces both Ca ++ influx and release of stored Ca ++ , but the Ca ++ influx may depend on release of stored Ca ++ . Further studies are in progress to elucidate the roles of IP3, PKC, and VGCC in the response to PE, and the phenotype of the SON neurons in which the Ca ++ response to PE persists in the absence of extracellular Ca ++ . Supported by NIH RO1 NS27975.