Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats

P. M. Sonner, S. Lee, P. D. Ryu, S. Y. Lee, Javier Eduardo Stern

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We investigated here whether an opposing interplay between the subthreshold currents A-type potassium (IA) and T-type calcium (IT) influences membrane excitability in presympathetic neurones of the hypothalamic paraventricular nucleus (PVN) that innervate the rostral ventrolateral medulla (RVLM). Moreover, we assessed whether a shift in the balance between these two subthreshold currents contributed to increased neuronal activity in hypertension. To this end, we obtained simultaneous electrophysiological recordings, confocal Ca2+ imaging, and single-cell RT-PCR samples from identified PVN-RVLM neurones in sham and renovascular hypertensive rats. Our results indicate that IA and IT, displaying overlapping voltage-dependent and kinetic properties, are present in PVN-RVLM neurones. We found that the relative predominance of each current at hyperpolarized membrane potentials dictates whether PVN-RVLN neurones express a low-threshold spike (LTS) or a transient outward rectification (TOR). Moreover, we report the IA/IT balance to be correlated with the relative expression of Kv4.3 and Cav3.1 subunit mRNA within individual neurones. Pharmacological blockade of IA resulted in an enhanced IT-mediated LTS, as well as LTS-mediated somatodendritic Ca2+ transients. In hypertensive rats, we found a shift in the IT/IA balance, towards an IT predominance, due in part to a diminished Kv4.3 and enhanced Cav3.1 mRNA subunits expression. The imbalanced IT/IA relationship resulted in enhanced LTS, LTS-mediated somatodendritic Ca2+ transients, and increased firing activity in hypertensive rats. Taken together, our results support that a balanced IT/IA interaction influences membrane excitability and Ca2+ dynamics in PVN-RVLM neurones. Moreover, an imbalanced relationship favouring IT results in enhanced neuronal excitability and firing discharge in hypertensive rats, constituting thus a likely mechanism contributing to the characteristic sympathoexcitation observed in this disease.

Original languageEnglish (US)
Pages (from-to)667-683
Number of pages17
JournalJournal of Physiology
Volume589
Issue number3
DOIs
StatePublished - Feb 1 2011

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Paraventricular Hypothalamic Nucleus
Neurons
Messenger RNA
Membranes
Membrane Potentials
Potassium
Pharmacology
Hypertension
Calcium
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Physiology

Cite this

Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats. / Sonner, P. M.; Lee, S.; Ryu, P. D.; Lee, S. Y.; Stern, Javier Eduardo.

In: Journal of Physiology, Vol. 589, No. 3, 01.02.2011, p. 667-683.

Research output: Contribution to journalArticle

Sonner, P. M. ; Lee, S. ; Ryu, P. D. ; Lee, S. Y. ; Stern, Javier Eduardo. / Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats. In: Journal of Physiology. 2011 ; Vol. 589, No. 3. pp. 667-683.
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