An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and pre-sympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca2+ imaging to determine whether altered N-methyl-D-aspartate (NMDA) receptor-mediated changes in intracellular Ca2+ levels (NMDA-ACa2+) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ACa2+ in MNCs from HF when compared with sham rats. The enhanced NMDA-ACa2+ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca2+ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca2+ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ACa2+ signaling during HF are discussed.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|State||Published - May 8 2013|
ASJC Scopus subject areas
- Physiology (medical)