Permeability of the arachnoid and pia mater. The role of ion channels in the leptomeningeal physiology

Abstract

Purpose: The purpose of this paper is to study the ionic permeability of the leptomeninges related to the effect of ouabain (sodium-potassium-ATPase inhibitor) and amiloride (epithelial sodium channel (ENaC) inhibitor) on the tissue, as well as identify the presence of ion channels. Methods: Cranial leptomeningeal samples from 26 adult sheep were isolated. Electrophysiological measurements were performed with Ussing system and transmembrane resistance values (RTM in Ω*cm2) obtained over time. Experiments were conducted with the application of ouabain 10-3 M or amiloride 10-5 M at the arachnoidal and pial sides. Immunohistochemical studies of leptomeningeal tissue were prepared with alpha-1 sodium-potassium-ATPase (ATP1A1), beta-ENaC, and delta-ENaC subunit antibodies. Results: The application of ouabain at the arachnoidal side raised the transmembrane resistance statistically significantly and thus decreased its ionic permeability. The addition of ouabain at the pial side led also to a significant but less profound increment in transmembrane resistance. The addition of amiloride at the arachnoidal or pial side did not produce any statistical significant change in the RTM from controls (p>0.05). Immunohistochemistry confirmed the presence of the ATP1A1 and beta- and delta-ENaC subunits at the leptomeninges. Conclusions: In summary, leptomeningeal tissue possesses sodium-potassium-ATPase and ENaC ion channels. The application of ouabain alters the ionic permeability of the leptomeninges thus reflecting the role of sodium-potassium-ATPase. Amiloride application did not alter the ionic permeability of leptomeninges possibly due to localization of ENaC channels towards the subarachnoid space, away from the experimental application sites. The above properties of the tissue could potentially be related to cerebrospinal fluid turnover at this interface. © 2012 Springer-Verlag.