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expression and function over time with direct effects, like changed
electrophysiological properties, a putative different behavior toward
interaction partners or a putative enhancement or suppression by
certain agents, and chronic effect depending on long-lasting changes
or on alteration of channel expression.
3.2. Ion Channel
Expression in Healthy
Vessels
For assessment of changes in ion channels expression, knowledge
about ion channel expression in healthy vessels is crucial. Only few
studies addressed ion channel expression in cerebral arteries:
Transcripts of the voltage-gated K
+
channel subunit K
v
1.1-K
v
1.6,
K
v
2.1, and K
v
2.2 were detected in healthy rat cerebral vessels but
only the K
v
1.2, K
v
1.5, and K
v
2.1 subunits were found to be
expressed (
21, 22
). Furthermore, ATP-sensitive K
+
channels
(among other: Kir6.1/SUR2B KATP channels, reviewed in refs.
(
23, 24
)), large conductance Ca
2+
-activated K
+
channels (BK
Ca
)
and inwardly rectifying K
+
channels (Kir) were proven (
25, 26
).
For voltage-gated Ca
2+
channels, L-type Ca
2+
channel were tradi-
tionally believed to control calcium infl ux in myocytes of cerebral
arteries, but two recent studies showed expression of various iso-
forms. In basilar myocytes of healthy dogs, Nikitina et al. (
27
)
identifi ed besides the L-type subunits Ca
v
1.2 and Ca
v
1.3 also the
Ca
v
2.2 subunit (N-type calcium channel) and the T-type subunits
Ca
v
3.1 and Ca
v
3.3. In rat basilar arteries, the Ca
v
1.2, an alternative
splice variant of Ca
v
1.2 containing exon 9*, Ca
v
1.3, Ca
v
3.1, and
Ca
v
3.2 subunit were found to be strongly expressed besides a weak
expression of the Ca
v
2.3 subunit (
28
).
In response of SAH, voltage-gated K
+
channel (K
v
) are functionally
impaired and expression of the K
v
1.5 and K
v
2 channels and K
v
-
mediated currents are markedly reduced (
4, 5, 19, 29, 30
). While
expression of large conductance Ca
2+
-activated K
+
channels (BK
ca
)
were unchanged after SAH, expression of Kir channels (Kir 2.1
subunit) was found to be increased which might be a compensa-
tory mechanism (
29, 31
). Changes of Ca
2+
channel expression in
response to SAH occur later and have only partially been subjected.
The recent studies analyzing expression of Ca
2+
channels during
vasospasm only carried out a molecular analysis for the Ca
v
1.2
(L-type calcium channel) and the Ca
v
2.3 subunit (E-/R-type cal-
cium channels) in cerebral arteries (
32, 33
). In a rabbit model,
cerebral arteries of healthy animals solely express Ca
v
1.2 Ca
2+
chan-
nels. Here, Ca
2+
infl ux after pressure-induced vasospasm depends
on L-type Ca
2+
channels and spasm could completely reversed
by the L-type Ca
2+
channel blocker diltiazem (
32
). In contrast after
SAH, oxy-hemoglobin induces an upregulation of the Ca
v
2.3 sub-
unit and a downregulation of Ca
v
1.2 in small arterial vessels
and cytoplasmatic Ca
2+
infl ux is mediated by E-/R-type Ca
2+
chan-
nels in up to 20%. These “resistant” Ca
2+
currents were not assess-
able for L-type Ca
2+
channel blockers (
33
). Furthermore,
oxy-hemoglobin leads to a reduced sensitivity of L-type Ca
2+
3.3. Changes in Ion
Channel Expression
Following SAH
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