Sustained depolarizing shift of the GABA reversal potential by glutamate receptor activation in hippocampal neurons.

The inhibitory action of GABA is a consequence of a relatively hyperpolarized Cl(-) reversal potential (E(Cl)), which results from the activity of K(+)-Cl(-) cotransporter (KCC2). In this study we investigated the effects of glutamate and glutamatergic synaptic activity on E(Cl). In dissociated culture of mature hippocampal neurons, the application of glutamate caused positive E(Cl) shifts with two distinct temporal components.

The Na(+)/H(+) exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons.

The effects of pH(i) on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were studied in mechanically dissociated CA3 pyramidal neurons, by use of ammonium prepulse and whole-cell patch-clamp techniques, under the voltage-clamp condition. NH(4)Cl itself, which is expected to alkalinize pH(i), increased GABAergic mIPSC frequency in a concentration-dependent manner. In contrast, NH(4)Cl decreased mIPSC frequency, either in the presence of 200 microm Cd(2+) or in Ca(2+)-free external solution, suggesting that intraterminal alkalosis decreased GABAergic mIPSC frequency while [NH4(+)] itself may activate Ca(2+) channels by depolarizing the terminal.

Substance P abolishes the facilitatory effect of ATP on spontaneous glycine release in neurons of the trigeminal nucleus pars caudalis.

Glycine release was facilitated by the activation of presynaptic ATP receptors (P(2X)-type) in a preparation of dissociated trigeminal nucleus pars caudalis neurons in which the native synaptic boutons were preserved. The action of ATP was completely blocked by substance P (SP) without alteration of the miniature IPSC (mIPSC) amplitude distribution. SP itself had no effect on mIPSC frequency or amplitude.

Quantitative assessment of a circulating depolarizing factor in shock.

Sustained depolarization of cell membranes and cellular edema are known to accompany various forms of circulatory shock and probably contribute to hypovolemia and cellular dysfunction. It has been proposed that a circulating protein is responsible for these effects. In the present study we have confirmed the existence of a circulating depolarizing factor (CDF) in hemorrhagic shock, burn shock, sepsis, and cardiopulmonary bypass.

Regulatory volume decrease and intracellular Ca2+ in murine neuroblastoma cells studied with fluorescent probes.

The possible role of Ca2+ as a second messenger mediating regulatory volume decrease (RVD) in osmotically swollen cells was investigated in murine neural cell lines (N1E-115 and NG108-15) by means of novel microspectrofluorimetric techniques that allow simultaneous measurement of changes in cell water volume and [Ca2+]i in single cells loaded with fura-2. [Ca2+]i was measured ratiometrically, whereas the volume change was determined at the intracellular isosbestic wavelength (358 nm). Independent volume measurements were done using calcein, a fluorescent probe insensitive to intracellular ions.

Calcium currents, transmitter release and facilitation of release at voltage-clamped crayfish nerve terminals.

1. The presynaptic terminals at crayfish (Procambarus spp.) opener neuromuscular junctions were voltage clamped.

Presynaptic calcium currents at voltage-clamped excitor and inhibitor nerve terminals of crayfish.

1. A two-electrode voltage clamp was used to record calcium currents from the excitatory and inhibitory nerve terminals that innervate the crayfish (Procambarus spp.) opener muscle.

Diet, aging, and cancer.

As we consider the epidemiologic evidence on diet-cancer associations, we should keep in mind the geographical differences in cancer incidence that stimulated us to look for a diet-cancer link in the first place. For many cancers, the variation in geographic incidence is in the range of an order of magnitude (see Table 2). Thus, if variation in dietary components are primarily responsible for these huge geographic variations in cancer incidence, then the effect of dietary components will not be subtle.

Presynaptic calcium-activated potassium channels and calcium channels at a crayfish neuromuscular junction.

1. We used a two-microelectrode current clamp to investigate various characteristics of the Ca(2+)-activated K+ conductance [gK(Ca)] and Ca2+ conductance (gCa), and transmitter release in presynaptic terminals of excitatory neuromuscular junctions in the crayfish walking leg. 2.

Streaming potentials reveal a short ryanodine-sensitive selectivity filter in cardiac Ca2+ release channel.

Single cardiac sarcoplasmic reticulum Ca2+ release channels were reconstituted into planar bilayer membranes. Streaming potentials were measured in osmotically asymmetric solutions as a shift in the reversal potential. Potential changes induced by water movement through the bilayer (concentration polarization) and reduced ion activity in the concentrated non-electrolyte solutions were determined using valinomycin.

Contrasting actions of cocaine, local anaesthetic and tetrodotoxin on discharge properties of rat aortic baroreceptors.

1. Effects of cocaine, lignocaine, benzocaine and tetrodotoxin (TTX) on the simultaneously measured pressure- and diameter-discharge frequency relations of single fibre baroreceptors were compared in rat in vitro aortic arch-aortic nerve preparations. 2.

Residual free calcium is not responsible for facilitation of neurotransmitter release.

An increase in internal free calcium ([Ca2+]i) in the presynaptic terminal is often assumed to directly produce facilitation of neurotransmitter release. Using a Ca(2+)-activated potassium conductance as a bioassay for free [Ca2+]i in the presynaptic terminal of the crayfish (Procambarus clarkii) opener neuromuscular junction, we now demonstrate that free [Ca2+]i has a decay time constant (tau) of 1-4 msec, whereas facilitation of neurotransmitter release has a decay tau of 7-43 msec. In addition, facilitation of neurotransmitter release can be markedly different at times when free [Ca2+]i values and presynaptic membrane voltages are equal.

A community-based epidemiologic study of health sequelae of exposure to hydrofluoric acid.

An accident at an oil refinery in Texas City, Texas, released around 40,000 lb of hydrogen fluoride, exposing the community to the highly toxic and corrosive substance. A population-based epidemiologic study was conducted to evaluate the impact of the accident on the health of the community. Exposure assessment was done using a multipronged approach through a door-to-door survey of 10,811 individuals.

Effects of osmotic stress on mast cell vesicles of the beige mouse.

The large size of the vesicles of beige mouse peritoneal mast cells (4 microns in diameter) facilitated the direct observation of the individual osmotic behavior of vesicles. The vesicle diameter increased as much as 73% when intact cells were perfused with a 10 mM pH buffer solution; the swelling of the vesicle membranes exceeded that of the insoluble vesicle gel matrix, which resulted in the formation of a clear space between the optically dense gel matrix and the vesicle membrane. Hypertonic solutions shrank intact vesicles of lysed cells in a nonideal manner, suggesting a limit to the compressibility of the gel matrix.

Presynaptic facilitation at the crayfish neuromuscular junction. Role of calcium-activated potassium conductance.

Membrane potential was recorded intracellularly near presynaptic terminals of the excitor axon of the crayfish opener neuromuscular junction (NMJ), while transmitter release was recorded postsynaptically. This study focused on the effects of a presynaptic calcium-activated potassium conductance, gK(Ca), on the transmitter release evoked by single and paired depolarizing current pulses. Blocking gK(Ca) by adding tetraethylammonium ion (TEA; 5-20 mM) to a solution containing tetrodotoxin and aminopyridines caused the relation between presynaptic potential and transmitter release to steepen and shift to less depolarized potentials.

Calcium-activated potassium conductance in presynaptic terminals at the crayfish neuromuscular junction.

Membrane potential changes that typically evoke transmitter release were studied by recording intracellularly from the excitor axon near presynaptic terminals of the crayfish opener neuromuscular junction. Depolarization of the presynaptic terminal with intracellular current pulses activated a conductance that caused a decrease in depolarization during the constant current pulse. This conductance was identified as a calcium-activated potassium conductance, gK(Ca), by its disappearance in a zero-calcium/EGTA medium and its block by cadmium, barium, tetraethylammonium ions, and charybdotoxin.

Ionic control of the size of the vesicle matrix of beige mouse mast cells.

Isolated matrices of the giant secretory vesicles of mast cells of the beige mouse were reliably produced by the osmotic lysis of isolated vesicles. These matrices maintained their form, and their sizes were easily measured using Nomarski optics. The size of the matrix depended on the ionic composition of the bathing solution.

On the time course of surgically induced compensatory muscle hypertrophication of the rat plantaris muscle.

1. The time course of the hypertrophy and hyperplasia of the rat plantaris muscle was determined from measurements of total muscle mass and cross-section analysis of fixed muscle. 2.

Scaling of response scale adverbs among black-American adults.

Although some attention has been given to the scale characteristics of modifying adverbs in Likert scales, the existing work has been concerned primarily with majority group members. Toward the goal of identifying valid labels for use on Likert scales with black-American respondents, 105 black-American adults scaled each of 27 adverbs (e.g.

Assessing the functional status of older patients with chronic illness.

The purpose of this study was to investigate the value of using a validated functional assessment instrument, the Sickness Impact Profile (SIP), with older, chronically ill patients seeking care at the family physician's office. The SIP was completed by the patient and the family physician on patients 55 years of age or older who were seen at a family practice residency clinic. The study used stratified, random assignment in an experimental design to compare physician and patient reaction to the SIP.

The interaction of intracellular Mg2+ and pH on Cl- fluxes associated with intracellular pH regulation in barnacle muscle fibers.

The intracellular dialysis technique was used to measure unidirectional Cl- fluxes and net acid extrusion by single muscle fibers from the giant barnacle. Decreasing pHi below normal levels of 7.35 stimulated both Cl- efflux and influx.

Inhibition of sodium currents by local anesthetics in chloramine-T-treated squid axons. The role of channel activation.

In order to test the requirement of Na channel inactivation for the action of local anesthetics, we investigated the inhibitory effects of quaternary and tertiary amine anesthetics on normally inactivating and noninactivating Na currents in squid axons under voltage clamp. Either the enzymatic mixture pronase, or chloramine-T (CT), a noncleaving, oxidizing reagent, was used to abolish Na channel inactivation. We found that both the local anesthetics QX-314 and etidocaine, when perfused internally at 1 mM, elicited a "tonic" (resting) block of Na currents, a "time-dependent" block that increased during single depolarizations, and a "use-dependent" (phasic) block that accumulated as a result of repetitive depolarizations.

Simultaneous electrical and optical measurements show that membrane fusion precedes secretory granule swelling during exocytosis of beige mouse mast cells.

Mast cells show dramatic morphological changes when undergoing exocytosis. We have investigated whether the first of those morphological changes, swelling of the secretory granule, precedes--and therefore possibly initiates--secretion or whether it occurs after fusion of the granule and plasma membranes. We used cell membrane capacitance to detect the moment when granule and plasma membrane become continuous.