GROWTH-CONDITIONS DIFFERENTIALLY AFFECT THE CONSTITUTIVE EXPRESSION OF PRIMARY RESPONSE GENES IN CULTURED CEREBELLAR GRANULE CELLS

Cultured cerebellar granule cells underwent apoptotic degeneration whe n grown in medium containing 10 instead of 25 mM K+. Knowing that apop tosis is associated with changes in the expression of primary response genes, we have measured c-fos, zif/268, and c-jun mRNA levels during maturation of cultured granule cells grown in 10 or 25 mM K+. The cons titutive expression of c-fos and zif/268 was differentially regulated by extracellular K+ concentration at 5 days of maturation in vitro (DI V), when cells grown under suboptimal conditions (i.e. in 10 mM K+) ar e committed to degenerate. At this stage, c-fos mRNA levels were detec table only in cultures grown in 25 mM K+, whereas zif/268 mRNA levels were dramatically elevated in cultures grown in 10 mM K+. This provide s one of the few conditions in which c-fos and zif/268 are differentia lly regulated in nerve cells. Substantial changes in c-jun, or beta-ac tin mRNA levels were detectable only at 7 DIV, when the percentage of apoptotic cells had already reached a plateau in cultures grown in 10 mM K+. We speculate that changes in the expression of zif/268 are impo rtant in the gene program associated with the induction of apoptosis b y trophic deprivation in cultured neurons.