Augmented KCa2.3 Channel Feedback Regulation of Oxytocin Stimulated Uterine Strips from Nonpregnant Mice

Uterine contractions prior to 37 weeks gestation can result in preterm labor with significant risk to the infant. Current tocolytic therapies aimed at suppressing premature uterine contractions are largely ineffective and cause serious side effects. Calcium (Ca2+) dependent contractions of uterine smooth muscle are physiologically limited by the opening of membrane potassium (K+) channels. Exploiting such inherent negative feedback mechanisms may offer new strategies to delay labor and reduce risk. Positive modulation of small conductance Ca2+-activated K+ (KCa2.3) channels with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), effectively decreases uterine contractions. This study investigates whether the receptor agonist oxytocin might solicit KCa2.3 channel feedback that facilitates CyPPA suppression of uterine contractions. Using isometric force myography, we found that spontaneous phasic contractions of myometrial tissue from nonpregnant mice were suppressed by CyPPA and, in the presence of CyPPA, oxytocin failed to augment contractions. In tissues exposed to oxytocin, depletion of internal Ca2+ stores with cyclopiazonic acid (CPA) impaired CyPPA relaxation, whereas blockade of nonselective cation channels (NSCC) using gadolinium (Gd3+) had no significant effect. Immunofluorescence revealed close proximity of KCa2.3 channels and ER inositol trisphosphate receptors (IP3Rs) within myometrial smooth muscle cells. The findings suggest internal Ca2+ stores play a role in KCa2.3-dependent feedback control of uterine contraction and offer new insights for tocolytic therapies.

New Result on the Feedback Capacity of the Action-Dependent Dirty Paper Wiretap Channel

The Gaussian wiretap channel with noncausal state interference available at the transmitter, which is also called the dirty paper wiretap channel (DP-WTC), has been extensively studied in the literature. Recently, it has been shown that taking actions on the corrupted state interference of the DP-WTC (also called the action-dependent DP-WTC) helps to increase the secrecy capacity of the DP-WTC. Subsequently, it has been shown that channel feedback further increases the secrecy capacity of the action-dependent DP-WTC (AD-DP-WTC), and a sub-optimal feedback scheme is proposed for this feedback model. In this paper, a two-step hybrid scheme and a corresponding new lower bound on the secrecy capacity of the AD-DP-WTC with noiseless feedback are proposed. The proposed new lower bound is shown to be optimal (achieving the secrecy capacity) and tighter than the existing one in the literature for some cases, and the results of this paper are further explained via numerical examples.