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Subarachnoid Hemorrhage Suppresses K V 1 and K V 2 Currents via Different Mechanisms in Rat Parenchymal Arteriolar Myocytes
Author(s) -
Koide Masayo,
O'Connor Kevin P.,
Pappas Anthony C.,
Syed Arsalan U.,
Wellman George C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.678.11
Subject(s) - arteriole , depolarization , chemistry , myocyte , patch clamp , potassium channel , medicine , 4 aminopyridine , biophysics , endocrinology , electrophysiology , microcirculation , biology
Subarachnoid hemorrhage (SAH) leads to membrane potential depolarization in arteriolar myocytes and enhanced arteriolar tone in brain parenchymal arterioles (Nystoriak et al , 2011). However, the mechanism underlying this augmented constriction is currently unknown. Here, we studied the impact of SAH on voltage‐gated potassium (K V ) currents. In rat parenchymal arterioles from control animals, K V 1.2, 1.5, 2.1 and 2.2 mRNA was expressed, and K V 1 and K V 2 currents were detected by conventional whole cell patch clamp electrophysiology. Both K V 1 and K V 2 currents as well as total K V (4‐aminopyridine‐sensitive) currents were significantly suppressed in arteriolar myocytes after SAH, however K V channel subtype expression was not changed. Our previous work demonstrated that a blood component oxyhemoglobin causes K V current suppression through heparin binding EGF‐like growth factor (HB‐EGF). HB‐EGF caused significant K + current suppression in myocytes from control animals, but not after SAH. Further, HB‐EGF suppressed K + currents in the absence and presence of K V 2 channel inhibition, but failed to alter currents in the presence of 4‐aminopyridine or during K V 1 channel blockade. These data suggest SAH causes K V 1 current suppression through HB‐EGF shedding, while K V 2 current suppression is independent of the HB‐EGF pathway. Supported by NIH P01 HL095488, Totman Medical Research Trust and the Peter Martin Fund.