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

¹Center for Perinatal Biology, ²Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350

Submitted 13 February 2003 ; accepted in final form 8 April 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⁺ 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 large conductance Ca²⁺-activated K⁺ channels (BK_Ca) and voltage-activated K⁺ (K_V) channels. 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 >30% higher than in those of the adult (P < 0.05) and that these were predominately due to iberiotoxin-sensitive currents from BK_Ca channels. Excised, insideout membrane patches revealed nearly identical unitary conductances and Hill coefficients for BK_Ca channels. The plot of log intracellular [Ca²⁺] ([Ca²⁺]_i) versus voltage for half-maximal activation (V) yielded linear and parallel relationships, and the change in V for a 10-fold change in [Ca²⁺] was also similar. Channel activity increased e-fold for a 19 ± 2-mV depolarization for adult myocytes and for an 18 ± 1-mV depolarization for fetal myocytes (P > 0.05). However, the relationship between BK_Ca open probability and membrane potential had a relative leftward shift for the fetal compared with adult myocytes at different [Ca²⁺]_i. The [Ca²⁺] for half-maximal activation (i.e., the calcium set points) at 0 mV were 8.8 and 4.7 µM for adult and fetal myocytes, respectively. Thus the increased BK_Ca current density in fetal myocytes appears to result from a lower calcium set point.

patch clamp; perforated whole cell; inside-out patch; calcium set point; calcium-activated potassium channel

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