Developmental differences in Ca²⁺-activated K⁺channel activity in ovine basilar artery

Abstract

. Developmental differences in Ca 2ϩ -activated K ϩ channel activity in ovine basilar artery. Am J Physiol Heart Circ Physiol 285: H701-H709, 2003. First published April 10, 2003 10.1152/ajpheart.00138. 2003.-A primary determinant of vascular smooth muscle (VSM) tone and contractility is the resting membrane potential, which, in turn, is influenced heavily by K ϩ channel activity. Previous studies from our laboratory and others have demonstrated differences in the contractility of cerebral arteries from near-term fetal and adult animals. To test the hypothesis that these contractility differences result from maturational changes in voltage-gated K ϩ channel function, we compared this function in VSM myocytes from adult and fetal sheep cerebral arteries. The primary current-carrying, voltage-gated K ϩ channels in VSM myocytes are the large conductance Ca 2ϩ -activated K ϩ channels (BKCa) and voltage-activated K ϩ (KV) channels. We observed that at voltageclamped membrane potentials of ϩ60 mV in perforated whole cell studies, the normalized outward current densities in fetal myocytes were Ͼ30% higher than in those of the adult (P Ͻ 0.05) and that these were predominately due to iberiotoxin-sensitive currents from BKCa channels. Excised, insideout membrane patches revealed nearly identical unitary conductances and Hill coefficients for BKCa channels. The plot of log intracellular [Ca 2ϩ ] ([Ca 2ϩ ]i) versus voltage for halfmaximal activation (V1/2) yielded linear and parallel relationships, and the change in V1/2 for a 10-fold change in [Ca 2ϩ ] was also similar. Channel activity increased e-fold for a 19 Ϯ 2-mV depolarization for adult myocytes and for an 18 Ϯ 1-mV depolarization for fetal myocytes (P Ͼ 0.05). However, the relationship between BKCa open probability and membrane potential had a relative leftward shift for the fetal compared with adult myocytes at different [Ca 2ϩ ]i. The [Ca 2ϩ ] for half-maximal activation (i.e., the calcium set points) at 0 mV were 8.8 and 4.7 M for adult and fetal myocytes, respectively. Thus the increased BKCa current density in fetal myocytes appears to result from a lower calcium set point.

Perinatal hypoxia triggers alterations in K+channels of adult pulmonary artery smooth muscle cells

“…Moreover, in our model, the outward current measured in the perforated-cell configuration was greater in PASMC from mice born in hypoxia than in controls. Similar observation was also done in cerebral arteries between fetal and adult SMC, respectively (25). These data suggest that, in our model, perinatal hypoxia could disturb the transition between fetal and adult life and that adult PASMC from mice born in hypoxia could maintain some characteristics of fetal PASMC.…”

“…Our electrophysiological results showed that, in adult control PASMC, cell capacitance, reflecting cell membrane surface, was greater than that of mice born in hypoxia. Interestingly, in cerebral arteries, cell capacitance was also found to be higher in adults than in fetal SMC (25). Moreover, in our model, the outward current measured in the perforated-cell configuration was greater in PASMC from mice born in hypoxia than in controls.…”

“…K Ca channel activity was found to be modulated by their phosphorylation state. In cerebral arteries, the greater electrical activity observed in fetal than in adult cells (25) was attributed to a higher extent of BK Ca channel phosphorylation in fetal myocytes, resulting in a greater activation of these channels (26). Such modulation of phosphorylation extent could also be implicated in the increased BK Ca activity observed in adult PASMC of mice born in hypoxia compared with controls.…”

Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway

“…As reported with BK channels from sheep basilar artery myocytes ( Lin et al, 2003 ), cerebrovascular BK channel NP o continuously ran down after patch excision, reaching ‫ف‬ 62% of control after 30 min ( Fig. 6 A ).…”

Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

“…In perforated whole cell voltage-clamped preparations of normoxic fetal basilar artery myocytes, normalized outward current densities were ϳ30% greater than those of the adult (38). This greater outward current density resulted primarily from iberiotoxin-sensitive "big" K Ca (BK Ca ) channel currents.…”