Dysregulation of Neuronal Ca2+ Channel Linked to Heightened Sympathetic Phenotype in Prohypertensive States.

Here, we identify dysregulation of cyclic-nucleotide (CN)-linked neuronal Ca(2+) channel activity that could provide the trigger for the enhanced sympathetic neurotransmission observed in the prohypertensive state. Furthermore, we provide evidence that increasing cGMP rescues the channel phenotype and restores ion channel activity to levels seen in normal neurons. We also observed CN cross-talk in sympathetic neurons that may be related to a differential switching in phosphodiesterase activity. The presence of these early molecular changes in asymptomatic, prohypertensive animals could facilitate the identification of novel therapeutic targets with which to modulate intracellular Ca(2+) Turning down the gain of sympathetic hyperresponsiveness in cardiovascular disease associated with sympathetic dysautonomia would have significant therapeutic utility.