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Survival of Swiss-Webster mouse cerebellar granule neurons is promoted by a combination of potassium channel blockers

Anthony A Collins, Maureen K MK Larson, Jilleen E JE Pfaff, and Jane E JE Ishmael

Toxicol Lett 171(1-2):9 (2007) PMID 17532582

Cultured cerebellar granule neurons (CGN) are commonly used to assess neurotoxicity, but are routinely maintained in supraphysiological (25mM) extracellular K^+ concentrations [K^+]"o. We investigated the effect of potassium channel blockade on survival of CGN derived from Swiss-Webster mice in supraphysiological (25mM) and physiological (5.6mM) [K^+]"o. CGN were cultured for 5 days in 25mM K^+, then in 5.6mM K^+ or 25mM K^+ (control). Viability, assayed 24h later by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) reduction and by lactate dehydrogenase (LDH) release, was ~50% in 5.6mM K^+ versus 25mM K^+ (p.001), but nifedipine did not attenuate neuroprotection by K^+ channel blockers. Together, these results suggest that the survival of CGN depends on the K^+ permeability of the membrane rather than the activity of a particular type of K^+ channel, and that the mechanism of neuroprotection by K^+ channel blockers is different from that of elevated [K^+]"o.

DOI: 10.1016/j.toxlet.2007.04.004
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