These findings suggest that subjects with diabetes exhibit a lower skin blood flow and lower NO response to externally applied vibration than matched normal subjects.

Cnidocytes, the stinging cells of cnidarians, discharge nematocysts in response to physical contact accompanied by the stimulation of specific chemoreceptors. Cnidocytes in fishing tentacles of a sea anemone are now found to discharge nematocysts preferentially into targets vibrating at 30, 55, and 65 to 75 hertz. Moreover, in the presence of submicromolar concentrations of known chemosensitizers, such as N-acetylated sugars and mucin, these optima shift to 5, 15, 30, and 40 hertz, frequencies that correspond to the movements of swimming prey. Hence, chemoreceptors for these substances tune cnidocyte mechanoreceptors to frequencies that match the movements of the prey.

. 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.

In ovine basilar arterial smooth muscle cells (SMCs), the fetal "big" Ca2+-activated K+ (BK) channel activity is significantly greater and has a lower Ca2+ setpoint than BK channels from adult cells. In the present study, we tested the hypothesis that these differences result from developmentally regulated phosphorylation of these channels. Using the patch-clamp technique and a novel in situ enzymological approach, we measured the rates and extents of changes in BK channel voltage activation from SMC inside-out patch preparations in response to selective activation and inhibition of channel-associated protein phosphatases and kinases (CAPAKs). We show that BK channel activity is modulated during development by differential phosphorylation and that the activities of CAPAKs change substantially during development. In particular, excised membrane patches from adult SMCs exhibited greater protein kinase A activity than those from a fetus. In contrast, fetal SMCs exhibited greater protein kinase G activity and phosphatase activity than adult SMCs. These findings extend our previous observation that the BK channel Ca2+ setpoint differs significantly in adult and fetal cerebrovascular myocytes and suggest a biochemical mechanism for this difference. In addition, these findings suggest that the functional stoichiometry of CAPAKs varies significantly during development and that such variation may be a hitherto unrecognized mechanism of ion channel regulation.

Appropriate chemical stimulation of cnidocytes along with mechanical stimulation is required to trigger discharge of cnidae. It has been generally assumed that such chemosensitization is mediated via specific chemoreceptors. Such chemoreceptors and their complementary ligands have never been identified. We now identify two groups of naturally occurring substances that chemosensitize cnida discharge in the feeding tentacles of the sea anemone, Aiptasia pallida. In addition, using a novel technique to quantify cnida discharge we demonstrate that these chemosensitizers act through at least two distinct classes of receptors. One class is broadly specific toward a variety of amino and imino acids and histamine (Ko 5 = 1 \-30nM), but is competitively inhibited by antihistamines (K, = 0. 1 -7.4 nM). A second class is specific for N-acetylated sugars (K0.5 = 0.1-1.5 nM), but not affected by antihistamines. Presumably, these chemoreceptors detect specific substances from potential prey. Thus, cnidocytes are sensitized to discharge their cnidae in response to mechanical stimuli originating from the prey.