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Peptide Synthesis> | Preparation of vital coronal brain slices form PN13 and PN90 mice, as well as electrophysiological recordings and pharmacological experiments, were performed essentially as described11. For all details, see S1. Briefly, for pharmacology, slices were preincubated with 300nM isradipine to block LTCCs6 , or 10μM Z941 or Z944, respectively, to block TTCCs27, or with 10μM DNIP/srDNIP, a D2/NCS-1 interaction prevention peptide26, synthesised by Genscript (http://www.genscript.com/index.html), bath applied (in ACSF) for at least 30minutes prior to recordings, and throughout recordings. | Get A Quote |
The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary f... More