Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats.
Accumulating evidence supports a contribution of the hypothalamic paraventricular nucleus (PVN) to sympathoexcitation and elevated blood pressure in renovascular hypertension. However, the underlying mechanisms resulting in altered neuronal function in hypertensive rats remain largely unknown. Here, we aimed to address whether the transient outward potassium current (I(A)) in identified rostral ventrolateral medulla (RVLM)-projecting PVN neurones is altered in hypertensive rats, and whether such changes affected single and repetitive action potential properties and associated changes in intracellular Ca(2+) levels. Patch-clamp recordings obtained from PVN-RVLM neurons showed a reduction in I(A) current magnitude and single channel conductance, and an enhanced steady-state current inactivation in hypertensive rats. Morphometric reconstructions of intracellularly labelled PVN-RVLM neurons showed a diminished dendritic surface area in hypertensive rats. Consistent with a diminished I(A) availability, action potentials in PVN-RVLM neurons in hypertensive rats were broader, decayed more slowly, and were less sensitive to the K(+) channel blocker 4-aminopyridine. Simultaneous patch clamp recordings and confocal Ca(2+) imaging demonstrated enhanced action potential-evoked intracellular Ca(2+) transients in hypertensive rats. Finally, spike broadening during repetitive firing discharge was enhanced in PVN-RVLM neurons from hypertensive rats. Altogether, our results indicate that diminished I(A) availability constitutes a contributing mechanism underlying aberrant central neuronal function in renovascular hypertension.
Sonner
Patrick M
PM
Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 E. Galbraith Rd, Cincinnati, OH 45237, USA.
Filosa
Jessica A
JA
Stern
Javier E
JE
D000200:Action Potentials; D000818:Animals; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000503:physiopathology*; D011188:Potassium / Q000378:metabolism*; D017729:Presynaptic Terminals; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D011188:Potassium