Aim: 

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder targeting upper and lower motor neurons resulting in progressive muscle wasting and paralysis. The alteration of intracellular Ca²⁺ homeostasis is thought to have a key role in the disease process, independently of the cellular and molecular events initiating motor neuron degeneration in ALS. The aim of this study was to evaluate the role of voltage-gated calcium channels in primary cortical culture from an ALS mouse model (G93A) with the patch-clamp technique.

Methods: 

The total Ca²⁺ current density recorded in G93A cortical neurons (14.2 + 7.4 pA/pF) was significantly higher than in wild type neurons (10.7 + 4.9 pA/pF; p<0.01). To characterize the different Ca²⁺ current subtypes (L-, N-, P/Q- and R-type), we applied specific antagonists of voltage-dependent calcium channels.

Results: 

G93A cortical neurons showed a significant increase of the N-type (w-conotoxin GVIA –sensitive) current-density (5.0 + 2.6 pA/pF) with respect to control neurons (2.5 + 1.6 pA/pF; p< 0.01). These data were confirmed by immocytochemical analysis which demonstrated that N-type voltage-gated calcium channels were expressed more in G93A cortical neurons than in controls.

Conclusion: 

Our results suggest that the voltage-gated calcium channels are involved in the ALS etiopathology.