Paradoxical effects of a CACNA1A mutation on neurotransmitter exocytosis in hippocampal neurons

Background: Presynaptic P/Q type calcium channels mediate neurotransmitter release at synapses of the central and peripheral nervous system. Mutations in the underlying CACNA1A gene are associated with paroxysmal neurological disorders such as familial hemiplegic migraine type 1 (FHM), absence seizures and episodic ataxia. The S218L mutation results in severe FHM together with susceptibility to brain oedema. There is still an ongoing debate about whether CACNA1A mutations lead to gain- or loss-of-function of neurotransmission which have opposite implications for the pathophysiological understanding and therapeut…