Target‐derived factors regulate the expression of Ca(2+)‐activated K+ currents in developing chick sympathetic neurones.

Abstract

1. The functional expression of CaP-activated K+ currents (IK(Ca)) and voltage-activated Ca2+ currents (ICa) was examined using whole-cell recordings from chick lumbar sympathetic neurones developing in situ and under various conditions in vitro.2. Macroscopic IK(ca) was expressed at low current density (<0 01 mA cm-2) in neurones isolated at embryonic days 9-16 (E9-16). IK(ca) was expressed at high densities (>0 04 mA cm-2) at El 7-19. By contrast, there was no significant difference in ICa density between sympathetic neurones isolated at E13 and E18. 3. When sympathetic neurones were isolated at E13 and maintained in vitro for 5 days, IK (Ca) was expressed at a significantly lower density (< 0 01 mA cm-2) than in neurones isolated acutely at E18 (>0 04 mA cm-2). There was no difference in ICa density between neurones that developed in vitro and in situ. 4. When El 3 sympathetic neurones were cultured for 5 days in the presence of a confluent layer of ventricular myocytes, they expressed IK(Ca) at a high density (>0 04 mA cm-2), similar to that of E18 neurones that developed entirely in situ. Cardiac cell-conditioned medium produced similar effects. However, co-culture of sympathetic neurones with spinal cord explants did not allow for normal IK(ca) expression in vitro. 5. Culturing sympathetic neurones in the presence of 5 ng ml-' nerve growth factor (NGF) caused a significant increase in IK(ca) density but this effect was only seen in 50% of cells examined.6. The largest developmental changes in macroscopic IK(ca) occur several days after other K+ currents and ICa are expressed at maximal density. The normal developmental expression of IK(Ca) is dependent upon extrinsic factors, including target-derived differentiation factors. Different populations of neurones express differentensembles of voltage-and Ca2+-activated ion channels.Differences in the expression of ion channels have important functional consequences as they allow neurones to express a specific electrophysiological phenotype suitable for the appropriate processing of information. Moreover, ion channels play an important role in the development and differentiation of vertebrate neurones, including regulation of the dependence of neurones on neurotrophic factors, neurite outgrowth and guidance, and the expression of neurotransmitters and their metabolic enzymes (reviewed by Spitzer, 1991;Spitzer, Gu & Olson, 1994 Spitzer, 1991;Ribera & Spitzer, 1992). Instead, the various ion channels appear gradually at developmental stages, and in a sequence, specific for a given cell type. In many populations of vertebrate neurones, those ion channels that produce subtle effects on action potential waveform and in the patterns of action potential discharge are expressed later than those channels that are essential for the minimal manifestation of

Neuregulins stimulate the functional expression of Ca 2+ -activated K + channels in developing chicken parasympathetic neurons

“…This suggests that activation of erbB2 receptors causes a cascade of effects specific for a given cell type. In this regard, we have noted that ␤-NEU fails to stimulate I K [Ca] in developing chicken lumbar sympathetic ganglion neurons, which express erbB2 receptors that can be phosphorylated in response to ␤-neuregulins (33) as well as an I K[Ca] whose expression is regulated by soluble differentiation factors (36). Thus, neuregulins resemble the neurotrophins in that they produce a number of cell typespecific actions exerted over a wide range of time scales (42).…”

“…Currents were evoked in normal and Ca 2ϩ -free salines, and the net Ca 2ϩ -dependent currents were obtained by digital subtraction. Currents were normalized for cell size by computing soma surface area for each cell from its diameter as measured with an ocular micrometer (29,30,35,36). Data were analyzed by one-way ANOVA when multiple comparisons were made, followed by Bonferonni's t-test when significant differences were observed between groups.…”

Neurotrophins and target interactions in the development and regulation of sympathetic neuron electrical and synaptic properties

“…Less is known about the specific factors that control ion channel expression in the sympathetic nervous system, but target interactions are clearly important for the expression of A-type (I A ) and K Ca potassium currents in chick sympathetic neurons (Raucher and Dryer, 1994, 1995). Expression of I A in chick sympathetic neurons increases between E7 and E20 and neurons isolated and maintained in culture at E9 fail to develop I A normally (Raucher and Dryer, 1994).…”

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

“…In lumbar sympathetic neurons taken from E13 chick and cultured for 5 days, NGF increases calciumdependent potassium currents (IK Ca ) as analysed by wholecell recordings (Raucher and Dryer 1995). The bimodal distribution of the current densities in NGF-treated cultures, in which half of the neurons show large current amplitude, indicates the presence of different neuronal subpopulations.…”