Whole-Cell and Single-Channel Analysis of P-Type Calcium Currents in Cerebellar Purkinje Cells of Leaner Mutant Mice

The leaner (tgla) mutation in mice results in severe ataxia and an overt neurodegeneration of the cerebellum. Positional cloning has revealed that the tglamutation occurs in a gene encoding the voltage-activated calcium channel α1A subunit. The α1A subunit is highly expressed in the cerebellum and is thought to be the pore-forming subunit of P- and Q-type calcium channels. In this study we used both whole-cell and single-channel patch-clamp recordings to examine the functional consequences of the tglamutation on P-type calcium currents. High-voltage-activated (HVA) calcium currents were recorded from acutely dissociated cerebellar Purkinje cells of homozygous leaner (tgla/tgla) and age-matched wild-type (+/+) mice. In whole cell recordings, we observed a marked reduction of peak current density in tgla/tgla Purkinje cells (−35.0 ± 1.8 pA/pF) relative to that in +/+ (−103.1 ± 5.9 pA/pF). The reduced whole-cell current in tgla/tgla cells was accompanied by little to no alteration in the voltage dependence of channel gating. In both genotypes, HVA currents were predominantly of the ω-agatoxin-IVA–sensitive P-type. Cell-attached patch-clamp recordings revealed no differences in single-channel conductance between the two genotypes and confirmed the presence of three distinct conductance levels (9, 13–14, and 17–18 pS) in cerebellar Purkinje cells. Analysis of patch open-probability (NPo ) revealed a threefold reduction in the open-probability of channels in tgla/tgla patches (0.04 ± 0.01) relative to that in +/+ (0.13 ± 0.02), which may account for the reduced whole-cell current in tgla/tgla Purkinje cells. These results suggest that the tgla mutation can alter native P-type calcium channels at the single-channel level and that these alterations may contribute to the neuropathology of the leaner phenotype.

• Publication year

  1998

• Venue

  Journal of Neuroscience

• Publication date

  1998-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.18-19-07687.1998PMID 9742139PMCID PMC6793003
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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