AP Responses Research Articles

Patch pipettes are more useful than initially thought: simultaneous pre- and postsynaptic recording from mammalian CNS synapses in vitro and in vivo

Patch pipettes were designed, initially, for the purpose of recording ionic currents through individual channels in cell membranes using a single pipette placed on a muscle membrane [28]. Here, we could watch a single biological molecule as it changed its structure by opening and closing a transmembrane pore. For example, at acetylcholine (ACh) concentrations of about 1 μM or higher, the same molecule switches repeatedly between an open and several closed state(s) [32]. The formation of a GΩ-seal between pipette tip and membrane widened the field of ion channel research. Currents were recorded with submillisecond resolution to resolve short opening and closing events [11]. Combined with genetic manipulation of ion channels expressed heterologously in Xenopus laevis oocytes, this technique facilitated the first structure–function assignments of ion channels. Single amino acids in putative pore-forming domains could be exchanged, and the subsequent effect on ion flows could be directly measured [20]. Finally, current recordings could be made from cell compartments such as the dendrite and terminal of a nerve cell. “Patch pipettes are, however, more useful than initially thought.” (Fred Sigworth) The whole-cell recording configuration also opened up a new field of research into the synapses of the mammalian central nervous system (CNS). In conjunction, the development of novel in vitro brain slice preparations and new visualization techniques in slices [12, 36] allowed us to characterize the properties of synapses in anatomically identified CNS pathways. Most useful were simultaneous whole-cell recordings made from cell pairs under visual control in combination with post hoc reconstructions of dendrites and axons of the two cells [26]. I will review the results we obtained by simultaneous pair recordings from preand postsynaptic CNS neurons and anatomical reconstructions. Each of the synapses we studied has a different function, and each is favorable to examine one particular aspect of synaptic function. One question relating to the properties of synapses in a neuronal network is how they might contribute to the magnitude and variability of AP responses observed in sensory systems. Unit recordings from single cells in sensory cortices indicate large differences both in the strength (efficacy) and trial-to-trial variability of suprathreshold responses. The contribution of synapses to this variability in particular is, so far, not well understood. By comparing three different synapses that are components of sensory pathways, we illustrate how one might be able to identify their contribution to the reliability of sensory representations. The rationale of this approach is to compare in vivo the magnitude and variability of response to sensory stimuli at different stages of a pathway. Concomitantly, a particular synapse between two stages is studied in vitro to delineate factors that determine synaptic efficacy and reliability. We first studied in vitro a relay synapse in the acoustic pathway. Cell pairs form an axosomatic synapse where the Pflugers Arch Eur J Physiol (2006) 453:249–259 DOI 10.1007/s00424-006-0172-4

Corticotrope hypersecretion coupled with cortisol hypo-responsiveness to stimuli is present in patients with autoimmune endocrine diseases: evidence for subclinical primary hypoadrenalism?

In autoimmune polyglandular syndrome types 1, 2, and 4 primary adrenal insufficiency is present, but its diagnosis is often late. We investigated the function of the hypothalamic-pituitary-adrenal axis in a group of patients with autoimmune diseases (AP) without any symptoms and signs of hypoadrenalism. In 10 AP and 12 normal subjects (NS), we studied cortisol (F), aldosterone (A), and DHEA responses to 0.06 microg adrenocorticotropin (ACTH) (1-24) followed by 250 microg, ACTH and F responses to human corticotropin-releasing hormone (hCRH; 100 microg) and insulin tolerance test (ITT) (0.1 UI/kg). Basal F, A, DHEA, as well as urinary free cortisol and plasma renin activity levels in AP and NS were similar, whereas ACTH levels in AP were higher (P<0.05) than in NS. NS showed F, A, and DHEA response to both consecutive ACTH doses. In AP, the F, A, and DHEA responses to 250 microg ACTH were similar to those in NS, whereas the 0.06 microg ACTH dose did not elicit any significant response. The ACTH responses to hCRH and ITT in AP were higher (P<0.05) than in NS. The F response to hCRH in AP was lower (P<0.05) than in NS, whereas the F response to ITT in AP did not significantly differ from NS. Enhancement of both basal and stimulated corticotrope secretion coupled with reduced adrenal sensitivity to low ACTH dose is present in AP patients without symptoms and signs of hypoadrenalism. This functional picture suggests that normal adrenal secretion is maintained due to corticotrope hyperfunction, suggesting the existence of some subclinical primary hypoadrenalism.

Effect of recruitment method and setting on the composition of samples consisting of adult smokers

Objective This study aims to determine differences in samples of adult smokers recruited by passive or active recruitment in community pharmacy (PP and AP) or passive recruitment in general practice setting (PG), then comparing these samples to an unrecruited cohort of Dutch smokers. Methods The three recruited samples were compared on demographics, smoking behaviour, motivational determinants, stage of change and intention to use specific action plans when quitting using multinomial logistic regression analyses; this method was also used to assess whether recruitment affected the acquired samples concerning demographic variables compared with the cohort. PP, AP and PG response rates were compared with Tukey post hoc tests. Results Significant differences were found for both AP and PG smokers, compared with PP smokers. Most important results include a higher rate of pre-contemplators in the AP sample and a lower educational level in the PG sample. All recruited samples appeared to be significantly different from the cohort sample. Conclusion Recruitment method and primary care setting does influence the sample recruited, this should be taken into consideration when recruiting a specific sub-sample. Practice implications These results are valuable for researchers contemplating recruitment in a primary care setting.

Antibody Responses to Porphyromonas gingivalis Hemagglutinin A and Outer Membrane Protein in Chronic Periodontitis

Hemagglutinin and outer membrane protein (OMP) are major virulence factors associated with colonization of Porphyromonas gingivalis in the gingival crevice. The genes for the 200-kDa antigenic protein (200-kDa AP) and 40-kDa OMP of P. gingivalis have been successfully cloned. Additionally, the 200-kDa AP gene has been shown to constitute the hemagglutinin A (hagA) gene of P. gingivalis. Therefore, this study was constructed to evaluate the distributions and serum levels of immnoglobulin G (IgG) antibodies specific for 200-kDa AP and 40-kDa OMP in periodontitis patients. Fifty patients with chronic periodontitis and 59 controls without periodontal destruction were enrolled in this study. We cloned the genes for 200-kDa AP and 40-kDa OMP from P. gingivalis and constructed the purified recombinant proteins. Serum levels of IgG subclass antibodies specific for both recombinant 200-kDa and 40-kDa OMP were determined in patients and controls by an enzyme-linked immunosorbent assay (ELISA). The serum IgG subclass distribution for patients and controls was IgG1>IgG4>IgG2>IgG3 in the anti-200-kDa AP response, which was almost identical to that in the anti-40-kDa OMP response. The patient group showed significantly higher serum IgG responses to the 40-kDa OMP than the control group (P<0.01). In contrast, IgG subclass responses to the 200-kDa AP were not different between the patients and controls. Serum levels of antibodies reactive with both 200-kDa and 40-kDa proteins did not have a significant association with mean probing depth. These results suggested that serum IgG responses against P. gingivalis OMP rather than the hagA may be more active in chronic periodontitis.

Association study of 12 polymorphisms spanning the dopamine D2 receptor gene and clozapine treatment response in two treatment refractory/intolerant populations

Dopamine D(2) receptor blockade is the major basis for the antipsychotic action of typical antipsychotic drugs (AP) and a necessary but not sufficient basis for the antipsychotic action of atypical APs such as clozapine and other multireceptor antagonists which rely, in part, upon 5-HT(2A) antagonism. Genetic factors affecting the density and/or function of D(2) receptors may therefore affect AP response. This exploratory study investigates the effect of 12 single nucleotide polymorphisms (SNPs) spanning the entire dopamine D(2) gene on clozapine response in two distinct schizophrenic populations (Caucasian and African-American) refractory or intolerant to conventional APs. This study included 183 Caucasian and 49 African-American DSM-III-R or DSM-IV schizophrenics. Genotyping was determined by 5'-exonuclease fluorescence assays. Within each population genotype, allele, allele +/-, and haplotype frequencies were compared between responders and non-responders by X (2) tests. Linkage disequilibrium analysis was also performed. In the Caucasian sample, no significant associations were found for individual SNP tests; however, two haplotypes were identified as having significant protective effects on treatment outcome. In the African-American sample, individual SNP tests identified the Taq1A, Taq1B, and rs1125394 markers as being predictive of clozapine response. Haplotype analyses identified four protective haplotypes containing these SNPs. In addition, no association between the -141C Ins/Del site and clozapine response was found in either population. Interindividual variability in clozapine response among treatment refractory/intolerant patients is still not fully understood and likely involves multiple factors. This exploratory analysis suggests that the D(2) receptor gene may be one such factor.

Quasi–static studies of the deformation and failure of PBX 9501

This paper examines the influence of microstructure on the quasi–static failure of PBX 9501, a polymer–bonded explosive (PBX) manufactured for the Los Alamos National Laboratory in America. Optical microscopy has been used to examine qualitatively cracked and pristine material. Consequent on the manufacturing process, the explosive crystals display angular features and natural facets. In addition, considerable growth twinning, internal defects and voidage has been observed. These defects are found significantly to alter the failure path. In common with other PBXs, failure paths tend to run around the long straight edges of the explosive filler and avoid regions of fine filler and binder. Explosive crystals were found to fracture due either to cracks propagating from another region or internal defects. These observations are confirmed by the use of high–resolution moire interferometry. This sensitive optical technique allows the deformation of the sample to be measured up to and including the point of failure. By taking white–light micrographs that are in exact registration with the measured displacement maps, the influence of the underlying microstructure can be seen.

Structure-activity relationships of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs) at P2 receptors in the rat mesenteric arterial bed.

1. Vascular effects of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs), novel families of naturally-occurring signalling molecules, were investigated in methoxamine preconstricted rat isolated perfused mesenteric arterial beds. 2. Three different types of response were elicited by Ap(n)As and Ap(n)Gs. Those with a short polyphosphate chain (n=2 - 3) elicited vasorelaxation. Ap(3)A was more potent than Ap(2)A, and both were more potent than the corresponding Ap(n)G. Relaxations to Ap(3)A and Ap(3)G, but not to Ap(2)A and Ap(2)G, were blocked by endothelium removal and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist. 3. Longer polyphosphate chain Ap(n)As and Ap(n)Gs (n=4 - 6) elicited dose-dependent vasoconstriction followed by prolonged vasorelaxation, with a potency order for both types of response of Ap(5)A> or =Ap(6)A>Ap(4)A. A similar order and potency was observed for Ap(n)Gs. Contractions and prolonged relaxations were blocked by PPADS and P2X(1) receptor desensitization with alpha,beta-methylene ATP (alpha,beta-meATP), and were largely endothelium-independent. 4. In the presence of alpha,beta-meATP rapid relaxations to contractile Ap(n)As and Ap(n)Gs (n=4 - 6) were revealed. 5. Gp(n)Gs were virtually inactive, except for Gp(2)G which elicited vasoconstriction via PPADS- and alpha,beta-meATP-sensitive smooth muscle P2X(1)-like receptors. 6. These data show that, as with Ap(n)As, the length of the polyphosphate chain (n) is an important determinant of the activity of Ap(n)Gs at P2 receptors in the rat mesenteric arterial bed. When the chain is short (n=2 - 3) the purines elicit rapid vasorelaxation, which for Ap(3)A and Ap(3)G is mediated via endothelial P2Y(1)-like receptors. When the chain is long (n=4 - 6) Ap(n)As and Ap(n)Gs elicit vasoconstriction via P2X(1)-like receptors, followed by prolonged endothelium-independent vasorelaxation. Rapid relaxation to contractile dinucleotides (n=4 - 6) is revealed by block of vasoconstriction. Regarding the purine moiety, one adenine is crucial and sufficient for vasoactivity as Gp(n)Gs were largely inactive, and Ap(n)As and Ap(n)Gs approximately equipotent.

4-Aminophthalimide derivatives as environment-sensitive probes

The potential of 4-aminophthalimide (AP) and its derivatives as fluorescence probes for organized media is highlighted. The fluorescence response of AP, as measured from the position of the fluorescence maximum, fluorescence intensity and lifetime, is highly sensitive to the polarity of the medium. The sensitivity of the fluorescence parameters is further enhanced due to the involvement of the emitting intramolecular charge transfer state in hydrogen bonding interaction with the solvent molecules containing hydroxyl groups. It is shown that the microheterogeneous environments of organized media such as cyclodextrins and micelles can be very conveniently monitored using this probe. The results of the investigations carried out employing AP and its derivatives as fluorescence probe molecules in these media clearly suggest that a combination of the hydrophobic interaction with the host media and hydrogen bonding interaction with the solvent molecules determine the location of the fluorophore, which in all cases is found to be the interfacial region separating the nonpolar core of the micelle or the cyclodextrin cavity and the polar aqueous environment. Guidelines for the design of probes of this class of systems for the nonpolar core region of the micelles are provided and possible ways to increase the sensitivity of the fluorescence response of the systems are suggested.

Cardiovascular effects of apraclonidine in the conscious dog

AbstractApraclonidine (p‐aminoclonidine) a recognized α2‐adrenergic agonist, has been approved for use with ocular laser surgery and is under consideration for use as a chronic treatment for glaucoma. The potential cardiovascular actions of apraclonidine in conscious animals has yet to be fully explored. The present studies were performed in conscious, chronically instrumented dogs to evaluate these possible cardiovascular effects. In a first study, apraclonidine was administered iv in dosages ranging from 5 to 200 μg. When administered by this route, apraclonidine elicited profound, but transient, cardiovascular actions. Mean arterial pressure (MAP) and left ventricular systolic pressure (LVSP) showed significant increases at dosages of 50–100 μg or higher, while heart rate (HR) showed a significant reduction. No variables had values significantly different from control values 60 min after administration. In a second study, apraclonidine was applied topically to either one or both eyes in total dosages of 125–1,000 μg. In contrast to iv administration, even with doses of up to 1,000 μg, topical apraclonidine administered in the eye elicited no significant change in cardiovascular variables. In the third set of studies, the neurotransmitters acetylcholine (1–10 μg/kg) and norepinephrine (0.2–2 μg/kg) were administered iv both before and 45 min after 500 μg apraclonidine was applied to the eye. Topical apraclonidine enhanced the mean AP response to norepinephrine by as much as 18% and the LVSP response to norepinephrine by as much as 17% No effect on the response to acetylcholine was seen. We conclude that all cardiovascular changes following iv apraclonidine can be attributed to its vasoconstrictor action with the consequent rise in MAP. The absence of measurable effects after topical application was likely due to a much slower entry into the circulation, although the vasoconstrictor action of apraclonidine after topical applications seemed to be additive to that of iv norepinephrine. © 1993 Wiley‐Liss, Inc.

Inheritance of the Reversal of O2 Response of Photosynthesis in a Flaveria linearis Mutant

A mutant plant of Flaveria linearis Lag. expresses reversed O(2) response of photosynthesis (i.e. its apparent photosynthesis is stimulated at atmospheric O(2) levels). The objectives of this study were to determine the genetic inheritance of this trait and to investigate the biochemical mechanism for its expression. The mutant plant was crossed reciprocally with a plant of the closely related species Flaveria oppositifolia (DC.) Rydb. and also with another plant of F. linearis. Data on O(2) inhibition of apparent photosynthesis were analyzed on F(2) and F(3) progeny from these F(1) hybrids. In addition, test crosses (mutant x F(1) hybrid) and S(1) progeny from the mutant plant were also analyzed. All F(1) hybrids expressed inhibition of apparent photosynthesis and their progeny segregated in acceptable 3:1 and 13:3 (normal:reversed) ratios. There was little effect of environment on expression of the reversed O(2) response. Selected F(2) plants and the original mutant plant produced progeny in normal:reversed ratios which indicated the trait is controlled by two major genes which show dominant and recessive epistasis. Plants with greater than 20 nanomoles per gram fresh weight per minute of fructose-1, 6-bisphosphatase activity in the cytosol had normal O(2) response of photosynthesis. However, when plants had less than 20 nanomoles per gram fresh weight per minute of this enzyme activity in the cytosol, the O(2) was normal in some and reversed in others. It is proposed that low fructose bisphosphatase activity in the cytosol is controlled by a recessive gene (fbp). A second dominant gene is speculated to be hypostatic to the normal fructose bisphosphatase gene and controls the expression of an unknown factor that determines whether O(2) response of AP is reversed in the presence of fbp (i.e. when fructose bisphosphatase activity is low).

The effect of coronary artery occlusion on the cardiovascular response to an aversive stress.

The cardiovascular response to a controlled aversive stress was investigated both before and during acute myocardial ischemia. Classical aversive conditioning (a 30-s tone reinforced with a 1-s shock) served as the model of stress while anterior wall myocardial ischemia was induced by the occlusion (hydraulic occluder) of the left anterior descending coronary artery. The conditional response consisted of significant increases (P less than 0.01) in mean arterial pressure (AP, 13.8 +/- 1.9 mm Hg, 14.3%), left ventricular (LV) dP/dtmax (1300 +/- 324 mm Hg/s, 34.7%) and heart rate (HR, 44 +/- 4 beats/min, 46.8%). Mean coronary vascular resistance significantly (P less than 0.01) increased first (CVR, 0.52 +/- 0.18 mm Hg/ml/min, 17.2%), then decreased (0.77 +/- 0.14 mm Hg/ml/min, 25.5%). In contrast, during acute myocardial ischemia both the HR and d(LVP)/dtmax conditional response were significantly reduced (P less than 0.01) by 58 and 54%, respectively (HR, 20.7 +/- 3.8 beats/min, d(LVP)/dt, 756 +/- 226 mm Hg/s). In addition, the initial CVR increase was virtually eliminated (0.13 +/- 0.10 mm Hg/ml/min, 74.0% reduction) while the CVR decrease was significantly reduced (P less than 0.01) by 48% (0.40 +/- 0.15 mm Hg/ml/min) during the coronary occlusion. The mean AP response, however, was not affected by myocardial ischemia. The pre-conditional stimulus cardiovascular variables were similarly unaffected by the coronary artery occlusion. Thus, coronary artery occlusion attenuated both the coronary and cardiac response elicited by an aversive stress. The mechanism mediating this inhibition of the conditional response remains to be determined but may involve the activation of vagal depressor reflexes during the acute ischemia.

Frequency specificity of the cochlear action potential varies with stimulus presentation rate

It is well documented that the amplitude of an averaged cochlear action potential decreases as the rate of stimulus presentation is increased. In the present study, frequency regions contributing to the AP elicited by tone burst stimuli at rates from 4 to 80/s have been investigated in guinea pigs using a tone masking procedure. Derived responses corresponding to specific regions were obtained by subtracting AP responses in the presence of a low‐level continuous masking tone from those in the absence of masker. This is a modification of the technique described by Hood et al. [J. Acoust. Soc. Am. Suppl. 1 81, S8 (1987)]. When stimulation rate is increased, the derived response amplitudes decreased near the probe frequency region, while amplitudes at outlying frequencies were less markedly changed. These data suggest the contribution to the AP from the region corresponding to the probe frequency becomes less at high stimulation rates. With an 80/s stimulation rate the contribution from this region is negligible. The degradation of frequency specificity of responses is presumed to arise from each stimulus acting as a “forward masker” for the following stimulus. To optimize the frequency specificity of AP responses to tone burst stimuli, the rate of presentation must therefore be considered. [Work supported by NIH.]

Rapidly fluctuating thresholds at the onset of experimentally-induced hydrops in the guinea pig.

Pigmented guinea pigs were chronically implanted bilaterally with a platinum electrode on each round window. After recovery the endolymphatic sac was destroyed and the duct blocked on one side only; the other side was employed as a control. The round window response thresholds on both sides were recorded several times per week over a three month period. There were three main results. A sensitivity loss of up to 20 dB was observed for frequencies between 250 Hz and 6.4 kHz within two weeks post-op. At the end of three months the threshold elevation for these frequencies was as much as 50 dB. On the other hand the thresholds for frequencies between 8 and 16 kHz remained within 10 dB of their pre-operative value for at least two months. The thresholds fluctuated with a shift of as much as 25 dB within 24 h. The threshold elevation was associated with a decrease in the latency, at threshold, of the round window AP response which at frequencies between 250 Hz and 6.4 kHz was as short as that for 8 kHz. This observation suggested that it was the base, only, of the cochlea which responded. The present study has indicated that experimentally induced endolymphatic hydrops in the guinea pig mimics well the progressive and fluctuating hearing loss characteristic of Ménière's disease.

Sound perception in the ultrasonic region.

The mechanism of ultrasonic perception was investigated electrocochleographically in guinea pigs (1) to compare AP responses in normal animals with those in kanamycin-poisoned animals with a damaged outer hair cell system; (2) and to analyse the masking property of continuous ultrasonic sound upon the AP evoked by burst stimuli within the auditory field. The study revealed several facts indicating the breakdown of cochlear sharp frequency analysis in the transduction of ultrasonic sound. We concluded that the sound perception in the ultrasonic region could be performed by the inner hair cell system without any enhancement or modulation of the outer hair cell system, which was regarded as an important process in a recent model of cochlear micromechanics.

A comparison of AP and ABR tuning characteristics in the guinea pig

AP and ABR tuning curves were measured using a forward‐masking paradigm in guinea pigs with chronically implanted electrodes. Measurements were made before exposure to wide‐band noise and at several intervals after exposure. The noise exposure was sufficient to produce temporary threshold shifts up to 60 dB lasting several days and resulted in a systematic widening of both AP and ABR tuning curves and a reduction in tip‐to‐tail ratios. No significant differences were found between simultaneously recorded AP and ABR tuning curves as measured by Q10, tip‐to‐tail ratio, or the slope of the tuning curves. Tuning curves obtained by measuring AP and ABR response latency as a function of masker level, showed similar form and changes with hearing loss to those based on amplitude of response. The similarities between AP and ABR tuning characteristics provide evidence that the ABR is sensitive enough to peripheral changes to be a useful tool in the study of auditory frequency selectivity.

Short-Latency Auditory Evoked Potentials: Fundamental Bases and Clinical Applications

This book presents an excellent introduction to theoretical issues, methodological considerations, and clinical applications of the auditory nerve (AP) and auditory brain-stem response (ABR). It is a 160-page paperback from the<i>Fundamentals of Communication Science Series</i>, and it is packed with useful, relevant, and clearly stated information. Any student, audiologist, resident, physician, or other practitioner will find this book extremely useful for developing a basic understanding of ABR principles as well as providing a good foundation for pursuing more advanced aspects of auditory evoked potentials. The book begins with a concise account of cochlear potentials and mechanisms relevant to the generation of the AP and ABR. An overview of methodological considerations is then presented, including nice descriptions of differential preamplifiers, types of stimuli, and filtering. The next two chapters cover descriptions of normal and clinical applications of the AP response in humans. The final two chapters cover normal descriptions of

Brainstem, whole-nerve AP and single-fiber suppression in the gerbil: normative data.

Suppression of gerbil brainstem responses (BSRs) and whole-nerve AP responses was studied by means of a forward masking procedure in which a tone-burst probe was preceded by a narrow-band masker. The effectiveness of the masker in reducing the brainstem response to the probe can be diminished by presenting a tone burst simultaneously with the masker. By varying the frequency and intensity of the third stimulus, BSR suppression areas can be determined. These flank the tails and high-frequency sides of BSR tuning curves in a manner similar to the suppression areas of AP tuning curves. The shapes and sizes of the BSR and AP suppression areas vary greatly across probe frequencies and animals. However, the lower boundaries of suppression areas associated with the tails of the tuning curves occur at similar absolute levels regardless of probe frequency or tuning curve shape. The BSR and AP suppression areas are in some respects similar to areas of two-tone rate suppression in single auditory nerve fibers of the gerbil.

Rat endometrial cells in primary culture: effects and interaction of sex hormones and vitamin D3 metabolite on alkaline phosphatase.

The present study was undertaken: 1) to investigate and compare the effects of two sex steroids, 17 beta-estradiol and progesterone, and two vitamin D3 metabolites, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1,25-dihydroxyvitamin D3 (1,25-OH)2D3) on the alkaline phosphatase activity (AP) of cultured endometrial cells of ovariectomized animals; 2) to see whether the in vitro or in vivo sex steroid pretreatment modifies the cellular AP responses to these vitamin D3 metabolites. Cells were cultured in Dulbecco's medium with 10% fetal calf serum until confluency and then for 18 h in a serum-free medium. All subsequent studies were performed in a fresh fetal calf serum-free medium. Results show that: 1) in endometrial cells from untreated ovariectomized rats, 17 beta-estradiol (10(-9) M) or progesterone (10(-9) M) induces increases in AP (40% or 30%) after 2- to 4-h incubation, respectively. A maximal increasing effect (20%) is observed with 24,25-(OH)2D3 (10(-9) M) after 4-h incubation contrasting with the total lack of action of 1,25-(OH)2D3 whatever the concentration (10(-13) to 10(-7) M) and the incubation time (1-18 h) tested. 2) After in vivo or in vitro pretreatment with each sex hormone taken separately, both 24,25-(OH)2D3 and 1,25-(OH)2D3 decrease AP whereas after pretreatment with sex steroids in association, these vitamin D3 metabolites induce an increase in AP. In conclusion, these data show that endometrial cell AP is sensitive to 24,25-(OH)2D3 and 1,25-(OH)2D3 and that the AP response of these cells is modulated by the presence of 17 beta-estradiol and/or progesterone.

Whole‐nerve response to tone bursts in the alligator lizard

The peripheral auditory system of the alligator lizard (Gerrhonotus multicarinatus) has been studied extensively; however, limited data are available for the whole‐nerve (AP) response. Could the AP serve as a convenient monitor of the condition of the ear during experimentation? AP responses to tone burst acoustic stimuli of various frequencies were recorded from the alligator lizard and three measures using the AP response were obtained. (1) Averaged suprathreshold AP responses were related to primary auditory nerve fiber activity. (2) AP thresholds were compared to single‐unit thresholds. (3) AP excitatory tuning curves were compared to single‐unit tuning curves. The good agreement between AP responses and single‐unit data indicate that the AP is a useful tool for measuring the physiology of the peripheral auditory system in the alligator lizard.

Relation between discharges in auditory nerve fibers and the whole-nerve response shown by forward masking: an empirical model for the AP.

Whole-nerve action potentials evoked by a standard click were recorded from a gross electrode on the RW and the discharges of auditory nerve fibers to the same standard click were recorded from micropipette electrodes in the auditory nerve. The effect of a preceding tone burst (2, 4, or 8 kHz) upon the responses was measured for forward-masker intensities from 20 to 80 dB SPL. All forward maskers reduced the discharges of auditory nerve fibers to the standard click with the greatest reduction occurring for fibers with characteristic frequencies (CFs) near the masker frequency. The 4- and 8-kHz forward maskers produced similar effects on N1, P1, and N2 of the RW response. However, the 2-kHz forward masker produced enhancement at P1 and N2 in the RW response to the standard click. An empirical summation model of estimated elemental waveforms at latencies dependent on CF produces synthesized AP response waveforms which are similar to the observed RW response. The model permits the exclusion of discharges from segments along the cochlear partition in a manner similar to the effect of a forward masker. Alterations in the synthesized waveforms due to the exclusion of segments are similar in direction to the alterations observed in the RW responses for forward masking.