TARGET-DERIVED FACTORS REGULATE THE EXPRESSION OF CA2+ ACTIVATED K+ CURRENTS IN DEVELOPING CHICK SYMPATHETIC NEURONS

1. The functional expression of Ca2+-activated K+ currents (I-k(Ca)) a nd voltage-activated Ca2+ currents (I-Ca) was examined using whole-cel l recordings from chick lumbar sympathetic neurones developing in situ and under various conditions in vitro. 2. Macroscopic I-K(Ca) was exp ressed at low current density (<0.01 mA cm(-2)) in neurones isolated a t embryonic days 9-16 (E9-16). I-K(Ca) was expressed at high densities (> 0.04 mA cm(-2)) at E17-19. By contrast, there was no significant d ifference in I-Ca density between sympathetic neurones isolated at E13 and E18. 3. When sympathetic neurones were isolated at E13 and mainta ined in vitro for 5 days, I-K(Ca) was expressed at a significantly low er density (< 0.01 mA cm(-2)) than in neurones isolated acutely at E18 (> 0.04 mA cm(-2)). There was no difference in I-Ca density between n eurones that developed in vitro and in situ. 4. When E13 sympathetic n eurones were cultured for 5 days in the presence of a confluent layer of ventricular myocytes, they expressed I-K(Ca) at a high density (> 0 .04 mA cm(-2)), similar to that of E18 neurones that developed entirel y in situ. Cardiac cell-conditioned medium produced similar effects. H owever, co-culture of sympathetic neurones with spinal cord explants d id not allow for normal I-K(Ca) expression in vitro. 5. Culturing symp athetic neurones in the presence of 5 ng ml(-1) nerve growth factor (N GF) caused a significant increase in I-K(Ca) density but this effect w as only seen in 50% of cells examined. 6. The largest developmental ch anges in macroscopic I-K(Ca) occur several days after other K+ current s and I-Ca are expressed at maximal density The normal developmental e xpression of I-K(Ca) is dependent upon extrinsic factors, including ta rget-derived differentiation factors.