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another potassium channel which depends upon both
membrane potential and the intracellular calcium concen-
tration to open are generally expressed after the delayed
rectifier (O'Dowd et al., 1988; Dourado and Dryer, 1992).
In some systems, the appearance of specific channels has
been suggested to play a role in generating spontaneous
activity that is essential for maturation of synaptic con-
nections (Vasilyev and Barish, 2002; Picken et al., 2003).
Neural tube stage
100 msec
Early tailbud stage
Significance of Calcium Channel Expression
Calcium currents that are activated by small depolar-
izatons, called low-voltage activated (LVA) or T currents , are
broadly expressed in developing tissue. As the nervous
system matures, there is an increasing prominence of
calcium channels that activate only when the cell is
greatly depolarized (Figure 8.C). These are referred to as
high-voltage activated (HVA) or N and L currents . When hip-
pocampal neurons from E19 rats are placed in a dissoci-
ated culture, only LVA currents are recorded at first.
However, HVA currents appear over the next few days
and become a major contributor (Yaari et al., 1987). Simi-
larly, it is the LVA calcium currents that are primarily
observed when neurons from chick dorsal root ganglia,
ciliary ganglia, or ventral horn are first recorded from
(Gottmann et al., 1988; McCobb et al., 1989). These are
overtaken by HVA currents within about 24-48 hours.
The initial appearance of LVA calcium channels
can contribute greatly to a neuron differentiation. For
example, spontaneous calcium transients in developing
Xenopus spinal neurons, largely carried by LVA calcium
channels, have been implicated in the acquisition of
GABAergic phenotype and process outgrowth (Spitzer,
1994). In fact, these calcium transients regulate the matu-
ration of electrical properties, including a switch in potas-
sium channel isoforms. The rate of activation for single
potassium channels also increases by two to three times
as Xenopus spinal neurons mature in vitro. This transition
in channel kinetics is dependent upon calcium influx and
can be induced by activation of a protein kinase C
(Desarmenien and Spitzer, 1991).
15 msec
Young larva
2.5 msec
FIGURE 8.B Action potentials are initally calcium-depend-
ent. (Top) When intracellular recordings were made from spinal
cord (sc) Rohon-Beard neurons in neural tube stage Xenopus
embryos, depolarizing current injection produces long-lasting
calcium action potentials. (Middle) In early tailbud embryos,
current injection evokes a mixed sodium/calcium response.
(Bottom) In the young larva, current evokes a brief sodium-
dependent action potential. (Adopted from Spitzer, 1981)
cell back to rest and limits the amount of calcium that
enters during an action potential.
The sodium and potassium currents, as measured in
dissociated Xenopus spinal neurons, increase dramatically
within about 24 hours of their terminal mitosis (O'Dowd
et al., 1988). Similar observations have been made in
explants of chick cortex (Mori-Okamoto et al., 1983). In
acutely dissociated rat cortical neurons, the sodium
current density increases six-fold during the first two
postnatal weeks (Huguenard et al., 1988). However, there
is no uniform order of channel appearance in the nervous
system. Chick motor neurons have significant sodium
and delayed rectifying potassium currents from the
outset, and there is a relatively late appearance of at least
one type of potassium channel, and two types of calcium
channel (McCobb et al., 1989; McCobb et al., 1990). Yet
Regulation of Ionic Channel Expression
The addition of new channels to the membrane is nec-
essary for most increases in current density. For example,
when Xenopus neurons were grown in the presence of
RNA or protein synthesis inhibitors, the transition from
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