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Am J Physiol Heart Circ Physiol (April 10, 2003). doi:10.1152/ajpheart.00138.2003
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Submitted on February 13, 2003
Accepted on April 8, 2003

Developmental Differences in Ca2+-Activated K+ (BKCa) Channel Activity in Ovine Basilar Artery

Mike T. Lin1, David A. Hessinger2, William J. Pearce1, and Lawrence D. Longo1*

1 Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA; Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA
2 Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA

* To whom correspondence should be addressed. E-mail: llongo{at}som.llu.edu.

A primary determinant of vascular smooth muscle (VSM) tone and contractility is the resting membrane potential, which, in turn, is influenced heavily by K+ 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+ channel function, we compared this function in VSM myocytes from adult and fetal sheep cerebral arteries. The primary current-carrying, voltage-gated K+ channels in VSM myocytes are the "big" or "maxi" calcium-activated K+ channels (BKCa) and voltage-activated K+ channels (KV). We observed that at voltage-clamped membrane potentials of +60 mV in perforated whole-cell studies, the normalized outward current densities in fetal myocytes were more than 30% higher than in those of the adult (P < 0.05), and that these were predominately due to iberiotoxin-sensitive currents from BKCa channels. Excised, inside-out membrane patches revealed nearly identical unitary conductances and Hill coefficients for BKCa channels. The plot of log[Ca2+]i vs. voltage for half-maximal activation (V1/2) yielded linear and parallel relationships, and the change in V1/2 for a 10-fold change in [Ca2+] were also similar. Channel activity increased e-fold for a 19 ± 2 mV depolarization for adult, and for an 18 ± 1 mV depolarization for fetal myocytes (P > 0.05). However, the relationship between BKCa open probability and membrane potential had a relative left shift for the fetal compared to adult myocytes at different [Ca2+]i. The [Ca2+] for half-maximal activation (i.e. the calcium set-points) at 0 mV, were 8.8 µM and 4.7 µM for adult and fetal myocytes, respectively. Thus, the increased BKCa current density in fetal myocytes appears to result from a lower calcium set-point.




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