| 17532582 |
Collins A, Larson MK, Pfaff JE, Ishmael JE: Survival of Swiss-Webster mouse cerebellar granule neurons is promoted by a combination of potassium channel blockers. Toxicol Lett. 2007 Jun 15;171(1-2):60-8. Epub 2007 Apr 24.
Cultured cerebellar granule neurons (CGN) are commonly used to assess neurotoxicity, but are routinely maintained in supraphysiological (25 mM) extracellular K (+) concentrations [K (+)](o). We investigated the effect of potassium channel blockade on survival of CGN derived from Swiss-Webster mice in supraphysiological (25 mM) and physiological (5.6 mM) [K (+)](o). CGN were cultured for 5 days in 25 mM K (+), then in 5.6 mM K (+) or 25 mM K (+) (control). Viability, assayed 24 h later by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) reduction and by lactate dehydrogenase (LDH) release, was approximately 50% in 5.6 mM K (+) versus 25 mM K (+) (p <.001). Potassium channel blockers, 2 mM 4-aminopyridine (4-AP), 2 mM tetraethylammonium (TEA) or 1 mM Ba (2+), individually afforded limited protection in 5.6 mM K (+). However, survival in 5.6 mM K (+) with a combination of 4-AP, TEA and Ba (2+) was similar to survival in 25 mM K (+) without blockers (p <.001 versus 5.6 mM K (+) alone). CGN survival in 25 mM K (+) was attenuated 25% by 2 microM nifedipine (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). |
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