Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage

Abstract

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is due to contraction of smooth muscle cells in the cerebral arteries. The mechanism of this contraction, however, is not well understood. Smooth muscle contraction is regulated in part by membrane potential, which is determined by K⁺ conductance in smooth muscle. Voltage-gated (Kv) and large-conductance, Ca²⁺-activated K⁺ (BK) channels dominate arterial smooth muscle K⁺ conductance. Vasospastic smooth muscle cells are depolarized relative to normal cells, but whether this is due to altered Kv or BK channel function has not been determined. This study determined if BK channels are altered during vasospasm after SAH in dogs. We first characterized BK channels in basilar-artery smooth muscle using whole-cell patch clamping and single-channel recordings. Next, we compared BK channel function between normal and vasospastic cells. There were no significant differences between normal and vasospastic cells in BK current density, kinetics, Ca²⁺ and voltage sensitivity, single-channel conductance or apparent Ca²⁺ affinity. Basilar-artery myocytes had no, small- or intermediate-conductance, Ca²⁺-activated K⁺ channels. The lack of difference in BK channels between vasospastic and control cells suggests alteration(s) in other K⁺ channels or other ionic conductances may underlie the membrane depolarization and vasoconstriction observed during vasospasm after SAH.

Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage

“…In contrast to the decrease in K V function, we previously reported that K Ca channels were not altered 7 days after SAH [7]. It is thus unlikely that a primary alteration in K Ca channel function contributes to vasospasm.…”

Reduced Ca2+ Spark Activity after Subarachnoid Hemorrhage Disables BK Channel Control of Cerebral Artery Tone

“…Blood Flow & Metabolism (2011) (Jahromi et al, 2008b). In this study, we show that decreased BK channel activity does contribute to enhanced pressure-dependent constriction of resistance-sized cerebral arteries from SAH model rabbits.…”

“…Decreased BK channel activity following SAH could lead to vasoconstriction and compromise cerebral autoregulation. However, BK channel properties and expression seem to be unaffected in the basilar arteries obtained from a canine SAH model (Jahromi et al, 2008b). In this study, we show that decreased BK channel activity does contribute to enhanced pressure-dependent constriction of resistance-sized cerebral arteries from SAH model rabbits.…”

Bilirubin Oxidation End Products Directly Alter K+ Channels Important in the Regulation of Vascular Tone

“…A transcript profiling study using a canine model of SAH involving autologous blood injection documented down regulation of Kv2.2 and upregulation of Kir2.1 but no change in expression of Slo1 or Cav1.2 (Aihara et al 2003). Using the same canine model of SAH, Jahromi et al showed that the BK channel activity in acutely dissociated basilar artery smooth muscle cells is unaltered (Jahromi et al 2008); however, the concentrations of BOXes were not measured in the study. How these findings using native cells harvested from the experimental SAH animals relate to our finding that BOXes regulate Slo1 is not clear.…”