Sue K. Donaldson

Inositol trisphosphate stimulates calcium release from peeled skeletal muscle fibers

The effects of inositol phosphates (tris (InsP3), bis (InsP2), mono (InsP)) on rabbit adductor magnus and soleus muscles were determined using mechanically peeled fibers (sarcolemma removed). Isometric force generation of each fiber was continuously monitored and was used along with 45Ca to detect calcium release from internal fiber stores. All experiments were conducted at a physiological Mg2+ concentration (10(-3) M) of the bathing solutions. The inositol phosphates did not directly activate the contractile apparatus. At bath concentrations of 100-300 microM, only InsP3 was capable of stimulating Ca2+ release. In contrast, 1 microM InsP3 maximally and selectively stimulated Ca2+ release when microinjected into the myofilament lattice. Calcium releasing effects of InsP2 and InsP were manifested at 10 microM when they were microinjected. The end-to-end internal Ca2+ release and subsequent fiber force generation stimulated by the locally applied microinjected InsP3 suggests that the InsP3-induced Ca2+ release mechanism may involve propagation, but not via the Ca2+-induced Ca2+ release, since procaine did not inhibit this response. These findings support the possibility that InsP3 plays a role in skeletal muscle excitation-contraction coupling.

Breakthroughs in scientific research: the discipline of nursing, 1960-1999.

The period of 1960 to 1999 was an era of evolution and rapid growth of scientific research in the discipline of nursing during which specific knowledge realms, or subfields of the discipline, emerged and scientific breakthroughs occurred. This review presents the milestones or scientific breakthroughs of the era in the context of the prevailing thinking within and beyond the discipline of nursing. The nature of each scientific breakthrough in nursing is characterized as to the transdisciplinary change in thinking brought about by the work. The pathfinders for each scientific breakthrough are identified as well as their pathfinding modes. Opportunities for future scientific breakthroughs in nursing are presented.

Genetic Research and Knowledge in the Discipline of Nursing

Nursing exists in a world in which an evidence-base for professional practice is required. The nursing knowledge base specific to genetics and health is currently not sufficient to support the expansion of nursing educational content and practice that is needed for health care of individual humans or families. Coordinated research, education, and clinical development is needed for nursing to meet its societal mandate for health care in response to the genetic revolution.

Skeletal muscle excitation-contraction coupling II

Porcine skeletal muscle fibers were studied to determine if the defect in malignant hyperthermia involves transverse tubule (TT) to sarcoplasmic reticulum (SR) communication. Pelled (mechanically skinned) skeletal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs were stimulated with Cl− to ionically depolarize transverse tubules and thereby trigger Ca2+ release from SR. Caffeine was used to directly stimulate the Ca2+-induced Ca2+ release mechanism (CaIR) of the sarcoplasmic reticulum. Calcium released from internal fiber stores was monitored as Ca2+-activated isomeric force generation in the form of tension transients. Cl−-induced tension transients result from a primary component of Ca2+ release which triggers a secondary CaIR component; CaIR and caffeine contractures were eliminated by procaine. The primary component of Cl−-induced SR Ca2+ release was indistinguishable for MHS and normal skeletal peeled fibers at all TT resting and Cl− stimulation conditions. Only the magnitude of the secondary CaIR component was significantly larger in MHS fibers. The [Ca2+] threshold for secondary CaIR was lowered by resting TT depolarization in both normal and MHS fibers. Conditions for resting TT hyperpolarization selectively reduced the magnitude of the secondary CaIR component of MHS fibers, making them indistinguishable from normal.

Forging today's practice-academic link: a new era for nursing leadership.

In rapidly evolving health care scenarios, it is more essential than ever to have nursing viewed as a profession that has its clinical practice and academic arms united. It is necessary to keep schools of nursing entwined with what is evolving clinically and to keep clinical nurses closely involved with trends and issues in contemporary nursing education. To address this need, top nursing leadership must point the way. This article details one such model that was developed at Johns Hopkins, linking the service and education activities through the Institute for Johns Hopkins Nursing, a vehicle created for this purpose. Both sides shared a vision, both sides contributed willingly, and both have realized positive returns.

Osteoporosis Panel Summary

THIS CONFERENCE BROUGHT TOGETHER clinical investigators; epidemiologists; representatives of government regulatory agencies, industry, and Institutional Review Boards; government scientists; ethicists; and concerned laypersons to address critical issues in the development of new therapies for osteoporosis to prevent bone fractures. The meeting was not intended to achieve consensus. Rather, the American Society for Bone and Mineral Research wished to highlight emerging concerns. Doing so now is timely because additional potentially effective approaches to the problems of diagnosis of osteoporosis and prevention and treatment of fragility fractures are being developed. The problem of osteoporosis is likely to become even greater as the world population ages. This panel report will summarize some of the key issues developed at the conference. Detailed analyses of these issues are presented in the accompanying manuscripts.

Commentary: The science of human health-domain structure and future vision.

The purpose of this article is to complement Heitkemper and Bond’s insightful article “State of Nursing Science: On the Edge” by providing an alternative view of the state of science in the discipline of nursing. A new model for the organization of the domains of the science, the unified domain model, is presented to display the substantive structure of the discipline of nursing. The justification for this new domain model comes from a recent review of the major breakthroughs in research (Donaldson 2000) and Heitkemper and Bond’s update of the cutting edge of the science. In this article, the science of nursing is distinguished as related to but separate from the profession of nursing both in terms of objectives and associated activities. The science realm of the discipline of nursing is renamed the science of human health to reflect the current state of scientific knowledge. The unified domain model creates an organizational structure for the science of human health through the combination of 2 distinct classifications of research domains: 1) the thematic health domains and 2) the person-based health domains. The model is employed using selected examples of existing research to demonstrate how it can be used as the basis for qualitative mapping of research programs. Qualitative mapping on the grid of the unified domain model facilitates the detection of gaps in knowledge in a domain and helps to identify new directions for scientists in the field. A vision for the future of the science is offered that emphasizes the need to relate the science of human health to the genetic revolution in biology to achieve the goal of knowledge that may be used as the basis for improvement of human health (Donaldson 1999). Science and Profession: Related but Distinct

Mechanisms of excitation-contraction coupling in skinned muscle fibers

Although the mechanisms underlying most aspects of excitation-contraction (EC) coupling in skeletal muscle are well understood, a very basic step, that of communication between the transverse tubule (TT) region of the plasmalemma and the terminal cisternae of the sarcoplasmic reticulum (SR), has not been elucidated. Several types of TT to SR communication have been proposed, including electrical, chemical, and mechanical coupling. Current evidence supports a combination of the latter two. Studies of single rabbit skeletal muscle fibers, skinned by peeling the sarcolemma, demonstrate that a chemical stimulus for SR Ca2+ release, inositol trisphosphate (InsP3), could play a role in skeletal EC coupling. InsP3 appears to open the same SR Ca2+ channel that is activated by caffeine, Ca2+, and depolarization of TTs; all of these stimuli are inhibited by the SR Ca2+ channel blocker ruthenium red.