Role of cell-cell interactions in the developmental regulation of Ca2+-activated K+ currents in vertebrate neurons

Abstract

The functional expression of the Ca2+‐activated K+ current (IK[Ca]) is dependent on cell‐cell interactions in developing chick autonomic neurons. In chick ciliary ganglion (CG) neurons, expression of macroscopic IK[Ca] coincides with the formation of synapses with target tissues. CG neurons that develop in vivo in the absence of normal target tissues fail to express functional IK[Ca], although voltage‐activated Ca2+ currents and most other ionic currents are expressed at normal amplitudes and densities. CG neurons placed in cell culture prior to formation of synapses with target tissues also fail to express macroscopic IK[Ca]. However, CG neurons cultured in the presence of a heat‐ and trypsin‐sensitive extract of target tissues express IK[Ca] at normal levels. Similarly, interactions with target tissue appear to regulate the expression of whole‐cell IK[Ca] in developing chick sympathetic ganglion neurons, although the relevant trophic factors appear to be different from those required by CG neurons. In addition to target tissue interactions, an intact preganglionic innervation is required for the normal in vivo development of IK[Ca] in chick CG neurons. The trophic effects of the afferent innervation do not require synaptic activation of the CG neurons, indicating secretion of a trophic factor, possibly an isoform of β‐neuregulin. The results are consistent with the hypothesis that target‐ and nerve terminal‐derived trophic factors interact at a posttranslational level in the regulation of a functional IK[Ca]. Together, this body of data demonstrates an essential role for cell‐cell interactions in the differentiation of neuronal excitability. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 23–36, 1998

Developmental Changes in Electrophysiological Properties and Synaptic Transmission in Rat Intracardiac Ganglion Neurons

“…Cd 2ϩ (100 M) inhibited spontaneous EPSPs and APs in neurons of two adults, two juveniles, and one neonatal. In contrast to previous reports (Edwards et al 1995;Selyanko 1992) no instances of spontaneous sustained rhythmical action potential discharge, akin to pacemaker-like activity, were recorded. Sustained repetitive discharge could be evoked in some neurons on injection of small depolarizing currents (data not shown).…”

“…ICGs of adult animals contain a heterogeneous population of neurons, identified on the basis of their electrical and synaptic properties (Edwards et al 1995;Selyanko 1992;Selyanko and Skok 1992). However, it is not known when the specification of neuronal subtypes occurs.…”

“…Synaptic activation of the neurons in the cardiac ganglia thus needs to be considered as part of this pathway from the brain to the heart. Several animal models have been used for studying synaptic responses in the mature, adult ICG: guinea pigs (Edwards et al 1995); dogs (Bibevski et al 2000;Xi-Moy et al 1993); pigs (Smith 1999); and rats, adult (Selyanko and Skok 1992) and neonatal (Seabrook et al 1990). Nerve-evoked responses were blocked by hexamethonium and so are mediated by nicotinic acetylcholine receptors (Bibevski et al 2000;Selyanko and Skok 1992).…”

β-Neuregulin-1 is required for the in vivo development of functional Ca 2+ -activated K + channels in parasympathetic neurons

“…The development of functional K Ca in chick CG neurons depends on trophic factors released from preganglionic nerve terminals and ocular target tissues (16,17). We have previously demonstrated that K Ca are regulated by target-derived TGF␤1/4, which stimulates the development of K Ca (24), and target-derived TGF␤3, which inhibits the development of K Ca (25).…”

“…13 and 14), including chick ciliary ganglion (CG) neurons (15). The development of K Ca in chick CG neurons is regulated by interactions with target tissues and preganglionic innervation (16,17). Functional K Ca are not present in CG neurons before synapse formation with target tissues (18) or in later-stage CG neurons that develop in vivo in the absence of either target tissues or preganglionic input (16).…”