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Lower Affinity of Isradipine for L-Type Ca²⁺ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease.

ABSTRACT: Ca²⁺-influx through L-type Ca²⁺-channels (LTCCs) is associated with activity-related stressful oscillations of Ca²⁺ levels within dopaminergic (DA) neurons in the substantia nigra (SN), which may contribute to their selective degeneration in Parkinson's disease (PD). LTCC blockers were neuroprotective in mouse neurotoxin models of PD, and isradipine is currently undergoing testing in a phase III clinical trial in early PD. We report no evidence for neuroprotection by in vivo pretreatment with therapeutically relevant isradipine plasma levels, or Ca_v1.3 LTCC deficiency in 6-OHDA-treated male mice. To explain this finding, we investigated the pharmacological properties of human LTCCs during SN DA-like and arterial smooth muscle (aSM)-like ac

SUBMITTER: Ortner NJ

PROVIDER: S-EPMC6596555 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Dataset Information

Lower Affinity of Isradipine for L-Type Ca²⁺ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease.

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Dataset Information

Lower Affinity of Isradipine for L-Type Ca2+ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease.

OmicsDI is part of the ELIXIR infrastructure

Tweets

Lower Affinity of Isradipine for L-Type Ca²⁺ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease.