Unmasking the functions of the chromaffin cell α7 nicotinic receptor by using short pulses of acetylcholine and selective blockers

Methyllycaconitine (MLA), α-conotoxin ImI, and α-bungarotoxin inhibited the release of catecholamines triggered by brief pulses of acetylcholine (ACh) (100 μM, 5 s) applied to fast-superfused bovine adrenal chromaffin cells, with IC50s of 100 nM for MLA and 300 nM for α-conotoxin ImI and α-bungarotoxin. MLA (100 nM), α-conotoxin ImI (1 μM), and α-bungarotoxin (1 μM) halved the entry of 45Ca2+ stimulated by 5-s pulses of 300 μM ACh applied to incubated cells. These supramaximal concentrations of α7 nicotinic receptor blockers depressed by 30% (MLA), 25% (α-bungarotoxin), and 50% (α-conotoxin ImI) the inward current generated by 1-s pulses of 100 μM ACh, applied to voltage-clamped chromaffin cells. In Xenopus oocytes expressing rat brain α7 neuronal nicotinic receptor for acetylcholine nAChR, the current generated by 1-s pulses of ACh was blocked by MLA, α-conotoxin ImI, and α-bungarotoxin with IC50s of 0.1 nM, 100 nM, and 1.6 nM, respectively; the current through α3β4 nAChR was unaffected by α-conotoxin ImI and α-bungarotoxin, and weakly blocked by MLA (IC50 = 1 μM). The functions of controlling the electrical activity, the entry of Ca2+, and the ensuing exocytotic response of chromaffin cells were until now exclusively attributed to α3β4 nAChR; the present results constitute the first evidence to support a prominent role of α7 nAChR in controlling such functions, specially under the more physiological conditions used here to stimulate chromaffin cells with brief pulses of ACh.

Tonic nicotinic modulation of serotoninergic transmission in the spinal cord

The spinal serotoninergic projection from the raphe magnus has been shown to modulate nociceptive inputs, and activation of this projection mediates nicotine-elicited analgesia. Here, we investigate the interactions between cholinergic and serotoninergic systems in the spinal cord, by conducting serotonin [5-hydroxytryptamine (5-HT)] efflux experiments on mouse spinal slices. At least three spinal populations of nicotinic receptors are distinguished that affect 5-HT release. The first could be directly located on serotoninergic terminals, is insensitive to nanomolar concentrations of methyllicaconitine (MLA), and may be subjected to a basal (not maximal) cholinergic tone. The second is tonically and maximally activated by endogenous acetylcholine, insensitive to nanomolar concentrations of MLA, and present on inhibitory neurons. The last is also present on inhibitory neurons but is sensitive to nanomolar concentrations of MLA and not tonically activated by acetylcholine. Multiple nicotinic acetylcholine receptor populations thus differentially exert tonic or not tonic control on 5-HT transmission in the spinal cord. These receptors may be major targets for nicotine effects on antinociception. In addition, the presence of a tonic nicotinic modulation of 5-HT release indicates that endogenous acetylcholine plays a role in the physiological regulation of descending 5-HT pathways to the spinal cord.

Raising the bar: the importance of hospital library standards in the continuing medical education accreditation process*

The Connecticut State Medical Society (CSMS) reviews and accredits the continuing medical education (CME) programs offered by Connecticut's hospitals. As part of the survey process, the CSMS assesses the quality of the hospitals' libraries. In 1987, the CSMS adopted the Medical Library Association's (MLA's) “Minimum Standards for Health Sciences Libraries in Hospitals.” In 1990, professional librarians were added to the survey team and, later, to the CSMS CME Committee. Librarians participating in this effort are recruited from the membership of the Connecticut Association of Health Sciences Librarians (CAHSL). The positive results of having a qualified librarian on the survey team and the invaluable impact of adherence to the MLA standards are outlined. As a direct result of this process, hospitals throughout the state have added staffing, increased space, and added funding for resources during an era of cutbacks. Some hospital libraries have been able to maintain a healthy status quo, while others have had proposed cuts reconsidered by administrators for fear of losing valuable CME accreditation status. Creating a relationship with an accrediting agency is one method by which hospital librarians elsewhere may strengthen their efforts to ensure adequate library resources in an era of downsizing. In addition, this collaboration has provided a new and important role for librarians to play on an accreditation team.

Enabling, empowering, inspiring: research and mentorship through the years*

The interrelationship between research and mentorship in an association such as the Medical Library Association (MLA) is revealed through the contributions of individuals and significant association activities in support of research. Research is vital to the well-being and ultimate survival of health sciences librarianship and is not an ivory tower academic activity. Mentorship plays a critical role in setting a standard and model for those individuals who want to be involved in research and, ultimately, for the preparation of the next generation of health sciences librarians. Research and mentorship are discussed in the context of personal experiences, scholarship, and problem solving in a practice environment. Through research and mentorship, we are enabled to enhance our services and programs, empowered to look beyond our own operations for information puzzles to be solved, and inspired to serve society by improving health.

The rise and fall of the medical mediated searcher

The relationship between the development of mediated online literature searching and the recruitment of medical librarians to fill positions as online searchers was investigated. The history of database searching by medical librarians was outlined and a content analysis of thirty-five years of job advertisements in MLA News from 1961 through 1996 was summarized. Advertisements for online searchers were examined to test the hypothesis that the growth of mediated online searching was reflected in the recruitment of librarians to fill positions as mediated online searchers in medical libraries. The advent of end-user searching was also traced to determine how this trend affected the demand for mediated online searching and job availability of online searchers. Job advertisements were analyzed to determine what skills were in demand as end-user searching replaced mediated online searching as the norm in medical libraries. Finally, the trend away from mediated online searching to support of other library services was placed in the context of new roles for medical librarians.