Carbachol triggers RyR-dependent Ca(2+) release via activation of IP(3) receptors in isolated rat gastric myocytes.

Possible interactions between different intracellular Ca(2+) release channels were studied in isolated rat gastric myocytes using agonist-evoked Ca(2+) signals. Spontaneous, local Ca(2+) transients were observed in fluo-4-loaded cells with linescan confocal imaging. These were blocked by ryanodine (100 microM) but not by the inositol 1,4,5-trisphosphate receptor (IP(3)R) blocker, 2-aminoethoxydiphenyl borate (100 microM), identifying them as Ca(2+) sparks. Caffeine (10 mM) and carbachol (10 microM) initiated Ca(2+) release at sites which co-localized with each other and with any Ca(2+) spark sites. In fura-2-loaded cells extracellular 2-aminoethoxydiphenyl borate and intracellular heparin (5 mg ml(-1)) both inhibited the global cytoplasmic [Ca(2+)] transient evoked by carbachol, confirming that it was IP(3)R-dependent. 2-Aminoethoxydiphenyl borate and heparin also increased the response to caffeine. This probably reflected an increased Ca(2+) store content since 2-aminoethoxydiphenyl borate more than doubled the amplitude of transients evoked by ionomycin. Ryanodine completely abolished carbachol and caffeine responses but only reduced ionomycin transients by 30 %, suggesting that blockade of carbachol transients by ryanodine was not simply due to store depletion. Double labelling of IP(3)Rs and RyRs demonstrated extensive overlap in their distribution. These results suggest that carbachol stimulates Ca(2+) release through co-operation between IP(3)Rs and RyRs, and implicate IP(3)Rs in the regulation of Ca(2+) store content.

Roles of norepinephrine and ATP in sympathetically evoked vasoconstriction in rat tail and hindlimb in vivo.

In anesthetized rats, we characterized the contributions of norepinephrine (NE) and ATP to changes in tail and hindlimb (femoral) vascular resistances (TVR and FVR, respectively) evoked by three patterns of sympathetic stimulation: 1) couplets (2 impulses at 20 Hz), 2) short trains (20 impulses at 20 Hz), and 3) a natural irregular pattern previously recorded from a sympathetic fiber innervating the rat tail artery. All stimuli evoked greater changes in TVR than FVR. Judging from the effects of the -adrenoceptor antagonist phentolamine, the purinergic receptor antagonist suramin, or ,-methylene ATP (which desensitizes P2X receptors), we propose that NE has a major role in the constriction evoked by the couplet, as well as by the short train and by the low- and high-frequency components of the natural pattern, but that considerable synergy occurred between the actions of ATP and NE. This contrasts with previous in vitro studies that indicated that ATP dominates vascular responses evoked by sympathetic stimulation with a few impulses at low frequency and that NE dominates responses to longer trains or at high frequencies.

"The Black Imprint of Sandals in White Mosaic Floors": H.D.'s Mythomystical Poetics

My dissertation examines the traces of inverse (mytho)mysticism, more synchronous with mythical alchemy than transcendent mystery, in H.D.’s mature work (1946-1961). Whereas H.D.’s earliest works respond to a fin de siècle occultism and a collective psyche troubled by the eschatological distress that, as Susan Acheson writes, “was widespread amongst modernist writers grappling with …world events and with the implications of Nietzsche’s inaugural annunciation of modernity in terms of the death of God” (187), her later oeuvre is dedicated to the same work of soul undertaken by the “secret cult of Night” in Vale Ave. Here, her thematic scope faces two ways: backward to ancient Greek mystery cults and their palingenesic rites and forward to depth psychologists searching for the Soul of the World. Vale Ave plays a pronounced role in my study as symbolic guide; in its seventy-four sequences the layering of time in the “trilogy” of past, present, and future that H.D. had explored during the years of the Second World War in order to get behind the fallen walls of cause and effect collapses into two distinct phases of human origin—“meeting” (evolution) and “parting” (involution)—and the poem invites Lilith and Lucifer to be its archetypal guides. My method for the study is imaginal, entering such disciplines as history, philosophy, and theology and bringing psychological understanding to them. John Walsh’s introduction to Vale Ave notes H.D.’s theme “that the human psyche exists in a dimension outside of time and space as well as within them. In Vale Ave, H.D. presents the extremity of this dual-dimensionality: metempsychosis” (vii). However, the concept that H.D. investigates is more than a literary processus of characters who adopt different masks and appear at various junctures in a chronological unwinding of history. I explore H.D.'s works as part of a Modernist tradition of writing “books of the dead” designed not to guide the soul after death, but to draw the gaze upon “a nearer thing,” as H.D. writes in Erige Cor Tuum Ad Me In Caelum, the wisdom intrinsic in the spirit of life itself.