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If transynaptic signals regulate ion channel matura-
tion, they remain largely unknown. However, the glyco-
protein that stimulates AChR synthesis in muscle cells,
neuregulin, can induce a twofold increase in sodium
channels (Corfas and Fischbach, 1993). Other well-
described growth factors, such as FGF, can upregulate the
density of calcium channels in dissociated cultures of hip-
pocampal neurons, and the effect requires protein syn-
thesis (Shitaka et al., 1996). Electrical activity itself may
affect the expression level of certain channels. Action
potential blockade delays or prevents the normal increase
in sodium and potassium current density in Xenopus
myocytes in vitro (Linsdell and Moody, 1995).
The extrinsic signals that regulate ion channel expres-
sion are beginning to be understood in parasympathetic
neurons of the chick ciliary ganglion. The expression of
an A-type (I A ) and a calcium-activated potassium current
(I K[Ca] ) is reduced when ciliary neurons are grown in dis-
sociated culture, in the absence of their target or pregan-
glionic afferents (Duorodo and Dryer, 1992). To determine
whether synaptic connectivity influences potassium
channel expression, in vivo manipulations were per-
formed in which either the optic vesicle containing the
target tissue was removed or a portion of the midbrain
primordium containing the preganglionic nucleus was
removed (Duorodo et al., 1994). The neurons were then
acutely dissociated so that whole-cell voltage-clamp
recordings could be obtained easily. The density of I A was
unaffected by either manipulation, although the channels
did appear to open and close more rapidly than normal.
In contrast, I K[Ca] was reduced by 90 to 100% following
either target removal or deafferentation. Blocking the
spontaneous activity of chick lumbar motor neurons does
lead to a dramatic reduction in I A expression, both in ovo
and in vitro (Casavant et al., 2004).
A factor has now been isolated from a target of the
ciliary ganglion, the iris, that is able to upregulate the
density of I K[Ca] (Subramony et al, 1996). When neurons are
cultured in the presence of iris extract, the density of I K[Ca]
reaches normal levels within 7 hours (Figure 8.D). This
factor turns out to be a TGFb 1 . When an antibody directed
against the TGFb family is added to iris extract or injected
into the eye, the expression of I K[Ca] is inhibited (Cameron
et al., 1998). Interestingly, transcripts of the calcium-
activated potassium channel are present in cultured
ganglia before the current can be recorded, and the effect
of iris extract does not require protein synthesis. However,
brief exposure to TGFb 1 also elicits a persistent increase
E4 chick embryo
Di I label
Dissociate
Record from
Di I -labeled
motor neurons
8
L
6
N
4
50 pA
T
25 ms
N
2
L
T
0
4
6
11
Embryonic age (days)
FIGURE 8.C Two calcium currents increase while a third
declines in developing spinal motor neurons. A. To obtain iden-
tified motorneurons, a dye (DiI) was injected into the leg bud,
and this dye was retrogradely transported by motor neurons.
Thus, when the tissue was dissociated, it was possible to iden-
tify motor neurons because they carried the DiI label. B. When
calcium currents were recorded from the dissociated motor
neurons, it was found that T-type calcium channels declined with
age, while N- and L-type channels increased. (Adopted from
McCobb et al., 1989)
calcium- to sodium-dependent action potentials is pre-
vented (Blair, 1983; O'Dowd, 1983). In like manner, tran-
scription blockers prevent the normal increase in
potassium current density (Ribera and Spitzer, 1989). The
signal to increase production of potassium channels is
present for only a brief period of time. A 9-hour exposure
to an RNA synthesis inhibitor prevents the normal
increase in potassium current density, even though RNA
synthesis resumes upon withdrawal of the inhibitor.
However, the appearance of A currents are not perma-
nently blocked by transcription inhibitors.
 
 
 
 
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