Regulation of intracellular free calcium in normal and dystrophic mouse cerebellar neurons.

We measured free intracellular calcium ([Ca2+]i) in cultured cerebellar granule cells from normal and mdx mice. Resting levels of ([Ca2+]i) were 24% higher in the dystrophic neurons (normal: 61.2 +/- 1.5 nM calcium, n = 104; dystrophic: 76.1 +/- 2.4 nM calcium, n = 136, P less than 0.01). Dystrophic neurons showed a significantly greater increase in ([Ca2+]i) in the presence of elevated (18 mM) extracellular calcium levels. Resting sodium levels ([Na+]i), however, were found to be similar in normal and dystrophic granule neurons. In addition, sodium influx rates after ouabain inhibition of the Na+/K+ ATPase were also identical. Therefore, the increased permeability of granule neurons was specific to calcium, and did not result from a non-selective cation-permeable conductance. Unlike granule cells, astrocytes do not express dystrophin. Glial cells from normal and dystrophic mice showed no difference in their resting free calcium levels or their response to a high calcium load. Thus, cerebellar granule neurons from mdx mice show a calcium-specific regulatory defect similar to that found in dystrophic muscle fibers, while cerebellar glial cells, which do not normally express dystrophin, have no such defect.