Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit.

摘要: The Ca2+ channel α1A-subunit is a voltage-gated, pore-forming membrane protein positioned at the intersection of two important lines research: one exploring diversity channels and their physiological roles, other pursuing mechanisms ataxia, dystonia, epilepsy, migraine. α1A-Subunits are thought to support both P- Q-type currents, but most direct test, null mutant, has not been described, nor it known which changes in neurotransmission might arise from elimination predominant delivery system excitatory nerve terminals. We generated α1A-deficient mice (α1A−/−) found that they developed rapidly progressive neurological deficit with specific characteristics ataxia dystonia before dying ≈3–4 weeks after birth. P-type currents Purkinje neurons cerebellar granule cells were eliminated completely whereas types, including those involved triggering transmitter release, also underwent concomitant density. Synaptic transmission α1A−/− hippocampal slices persisted despite lack P/Q-type showed enhanced reliance on N-type R-type entry. provide starting point for unraveling neuropathological human diseases by mutations α1A.