Unconjugated bilirubin modulates neuronal signaling only in wild-type mice, but not after ablation of the R-type/Cav 2.3 voltage-gated calcium channel.

Abstract:

INTRODUCTION:The relationship between blood metabolites and hemoglobin degradation products (BMHDPs) formed in the cerebrospinal fluid and the development of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been the focus of several previous studies, but their molecular and cellular targets remain to be elucidated. METHODS:Because BMHDP-induced changes in Cav 2.3 channel function are thought to contribute to DCI after aSAH, we studied their modulation by unconjugated bilirubin (UCB) in an organotypical neuronal network from wild-type (WT) and Cav 2.3-deficient animals (KO). Murine retinae were isolated from WT and KO and superfused with nutrient solution. Electroretinograms were recorded before, during, and after superfusion with UCB. Transretinal signaling was analyzed as b-wave, implicit time, and area under the curve (AUC). RESULTS:Superfusion of UCB significantly attenuated the b-wave amplitude in the isolated retina from wild-type mice by 14.9% (P < 0.05), followed by gradual partial recovery (P = 0.09). Correspondingly, AUC decreased significantly with superfusion of UCB (P < 0.05). During washout, the b-wave amplitude returned to baseline (P = 0.2839). The effects of UCB were absent in Cav 2.3-deficient mice, lacking the expression of Cav 2.3 as proofed on the biochemical level. CONCLUSIONS:Ex vivo neuronal recording in the murine retina is able to detect transient impairment of transretinal signaling by UCB in WT, but not in KO. This new model may be useful to further clarify the role of calcium channels in neuronal signal alteration in the presence of BHMDPs.

journal_name

CNS Neurosci Ther

authors

Albanna W,Neumaier F,Lüke JN,Kotliar K,Conzen C,Lindauer U,Hescheler J,Clusmann H,Schneider T,Schubert GA

doi

10.1111/cns.12791

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

222-230

issue

3

eissn

1755-5930

issn

1755-5949

journal_volume

24

pub_type

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