SAH-induced suppression of voltage-gated K(+) (K (V)) channel currents in parenchymal arteriolar myocytes involves activation of the HB-EGF/EGFR pathway.

Potassium channels play an important role in the regulation of arterial tone, and decreased activity of these ion channels has been linked to pial artery vasospasm after subarachnoid hemorrhage (SAH). Our previous work has shown that acute application of a blood component, oxyhemoglobin, caused suppression of voltage-gated K(+) (K(V)) channels through heparin-binding epidermal growth factor-like growth factor (HB-EGF)-mediated activation of epidermal growth factor receptor (EGFR). Using patch clamp electrophysiology, we have now examined whether this pathway of K(V) channel suppression is activated in parenchymal arteriolar myocytes following long-term in vivo exposure to subarachnoid blood. We have found that K(V) currents, but not large conductance Ca(2+) activated or inwardly rectifying K(+) channel currents, were decreased in parenchymal arteriolar myocytes freshly isolated from day 5 SAH model rabbits. Interestingly, parenchymal arteriolar myocytes from control animals were more sensitive to exogenous HB-EGF (half-maximal inhibitory concentration [IC(50)] 0.2 ± 0.4 ng/ml) compared to pial arterial myocytes (IC(50) 2.4 ± 1.3 ng/ml). However, HB-EGF and oxyhemoglobin failed to decrease K(V) currents in parenchymal arteriolar myocytes from SAH animals, consistent with EGFR activation and K(V) current suppression by SAH. These data suggest that HB-EGF/EGFR pathway activation contributes to K(V) current suppression and enhanced parenchymal arteriolar constriction after SAH.