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Developmental differences in Ca2+-activated K+ channel activity in ovine basilar artery
Mike T Lin1, David A Hessinger, William J Pearce
1Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Summary
Fetal sheep cerebral arteries show higher vascular smooth muscle contractility due to increased large conductance calcium-activated potassium (BKCa) channel activity. This heightened BKCa channel function in fetal myocytes results from a lower calcium set point, influencing resting membrane potential.
Area of Science:
- Physiology
- Cardiovascular Biology
- Developmental Biology
Background:
- Vascular smooth muscle (VSM) tone is regulated by membrane potential, influenced by potassium (K+) channel activity.
- Cerebral artery contractility differs between fetal and adult animals, suggesting maturational changes in ion channel function.
Purpose of the Study:
- To investigate maturational changes in voltage-gated K+ channel function in sheep cerebral arteries.
- To determine if differences in K+ channel function explain observed contractility variations between fetal and adult VSM myocytes.
Main Methods:
- Compared voltage-gated K+ channel function in VSM myocytes from fetal and adult sheep cerebral arteries using whole-cell and patch-clamp electrophysiology.
- Assessed large conductance Ca2+-activated K+ (BKCa) and voltage-activated K+ (KV) channel activity.
- Analyzed current densities, unitary conductances, channel activation kinetics, and calcium sensitivity.
Main Results:
- Fetal VSM myocytes exhibited >30% higher normalized outward current densities than adult myocytes, primarily from iberiotoxin-sensitive BKCa channels.
- BKCa channels showed similar unitary conductances and voltage-dependent activation slopes but a leftward shift in open probability for fetal myocytes.
- Fetal myocytes had a significantly lower calcium set point (4.7 µM) compared to adult myocytes (8.8 µM) at 0 mV.
Conclusions:
- Increased BKCa current density in fetal sheep cerebral arteries is attributed to a lower intracellular calcium threshold for channel activation.
- These maturational changes in BKCa channel function contribute to differences in VSM tone and contractility between fetal and adult cerebral arteries.