Running Head: KCa AND KV CHANNELS DURING DEVELOPMENT

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 th