Ion Channel Assessment - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 504

comparison to controls. Ion channels inhibitors should carefully be
selected due to their inhibition pattern to prevent unwanted side
effects. Furthermore, dosage and corresponding ED 50 values
should be considered. Importantly, nearly all ion channel inhibi-
tors show unspecifi c side reactions in high concentrations, like the
specifi c blocker of E-/R-type Ca 2+ channels inhibiting L-type Ca 2+
channels in high concentration over 200 nM.
Effects of ion channels, respectively, their blockage could be
monitored in different ways and depend on the analyzed question.
Often, functional analysis focuses on quantifi cation of the contri-
bution of ion channels due to cerebral vasospasm. Degree of vasos-
pasm can be analyzed histopathologically, in either in vivo or
in vitro models like isometric tension recordings or in vivo models
for example by imaging methods like the traditional X-ray angiog-
raphy or Doppler-Ultrasound measurement. These chapters were
considered to discuss vasospasm assessments (Chap. 47), neuroim-
aging assessments, X-ray and angiographic assessments and MRI
assessments of cerebral vasospasms (Chaps 58-60). But functional
analysis includes also other methods, like evaluation of mediated
currents or visualization of ion channel infl ux or effl ux. Especially
for voltage-gated Ca 2+ channels, calcium infl ux can be visualized be
specifi c dyes. Blockade of infl ux from the extracellular space allows
also assessment of cytoplasmatic calcium infl ux from intracellular
stores. Also these methods are presented elsewhere (Chap. 56 )

The physiological role of ion channels in cerebral vessels and in
particular their pathophysiological role during SAH-induced vasos-
pasm has not completely been elucidated and remains partially
unclear. Previous studies of the physiological role of potassium
channels revealed that they are involved in the maintenance of the
resting membrane potential of vascular myocytes, that they are
involved in limiting depolarization of the membrane potential by
repolarization through K+ effl ux and thus regulate diameter of
cerebral arteries ( 6, 21, 22 ). K ATP channels have shown to be
involved in vasodilatation, reactive hyperemia in cerebral circula-
tion, and cerebral autoregulation while their inhibition leads to
vasoconstrictions (reviewed in ref. ( 6 )). The role of Ca 2+ channels
remains unclear: Navarro-Gonzalez et al. ( 28 ) suggested that
L-type Ca 2+ channels were responsible for vasomotion, whereas
non-L-type Ca 2+ channel control the vascular tone. In contrast, an
alternative splice variant of Ca v 1.2 containing exon 9* was found
to be mainly involved in K + -induced arterial constriction ( 48 ).
After SAH, decrease and dysfunction of K v channels were men-
tioned to contribute partially to depolarization and to have a
smaller contribution toward maintenance of the membrane poten-
tial. Therefore, they may be involved in the genesis and mainte-
nance of cerebral vasospasm, also their role remains controversial
( 5 ). While BK Ca channels are unchanged after SAH, Kir channels

3.7. Physiological
Role of Ion Channels
in Cerebral Vessels
and Their
Pathophysiological
Role During
Vasospasm