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Biomedical subjects

N Stockbridge

Publications and source records attributed to N Stockbridge.

12 recordsLinked to original sources
PubMed1992

Potassium currents of rat basilar artery smooth muscle cells.

Primary isolates of smooth muscle cells from the basilar artery of the rat were studied using whole-cell and single-channel patch-clamp techniques. Two distinct potassium currents were characterized. With low intracellular calcium, depolarization above 0 mV elicited an outward current of a few hundred pA (at +120 mV) with sigmoidal onset and little inactivation during 1.25 s steps. This current was reduced by bath application of 1 mM procaine or 1 mM strychnine, but not by 500 nM charybdotoxin. These are characteristics of the delayed rectifier potassium current in other preparations. With higher intracellular calcium, depolarization above 0 mV elicited a non-inactivating potassium current of several nA (at +120 mV). This current persisted in the presence of 1 mM procaine or strychnine but was reduced by bath application of 100 nM charybdotoxin. In whole-cell recordings in which intracellular calcium was unbuffered with EGTA, spontaneous transient outward currents were manifest and displayed voltage dependence and tail currents similar to the calcium-dependent current. The spontaneous transient current and the calcium-dependent current had similar sensitivity to charybdotoxin. Cell-free membrane patches contained one or more channels of 220 pS (in solutions symmetrical with respect to potassium) with similar voltage and calcium dependence. These are characteristics of the large conductance calcium-activated potassium current in other preparations.

Animals↗
PubMed1992

Vasodilatation of canine cerebral arteries by nicorandil, pinacidil and lemakalim.

1. Nicorandil, pinacidil and lemakalim relaxed precontracted rings of canine cerebral artery. 2. The order of potency was lemakalim greater than nicorandil approximately equal to pinacidil, but all these agents were less effective than nimodipine. 3. The effects of nicorandil were inhibited by methylene blue but not by glibenclamide, while the effects of pinacidil and lemakalim were inhibited by glibenclamide but not by methylene blue. 4. Thus nicorandil probably causes relaxation mostly by effects on guanylate cyclase while lemakalim and pinacidil produce the same effect by action at ATP-dependent potassium channels.

Animals↗
PubMed1991

Effects of K+ channel agonists cromakalim and pinacidil on rat basilar artery smooth muscle cells are mediated by Ca(++)-activated K+ channels.

Whole-cell and cell-free inside-out patch-clamp recording techniques were used to examine the actions of potassium channel openers pinacidil and cromakalim in enzymatically isolated smooth muscle cells of rat basilar artery. Delayed rectifier and calcium-dependent potassium currents were identified from the whole-cell recordings. Only the calcium-dependent potassium current was increased by cromakalim and pinacidil. Recordings from inside-out membrane patches revealed a large conductance voltage- and calcium-dependent potassium channel, which was blocked by charybdotoxin but unaffected by ATP less than 10 mM. Cromakalim and pinacidil increased the open probability of this channel. On the basis of these results, we suggest that such drugs, acting on cerebral arterial smooth muscle cell potassium channels, may be of some benefit in the treatment of cerebral vasospasm following subarachnoid hemorrhage.

Animals↗
PubMed1991

Glibenclamide relaxes vascular smooth muscle constriction produced by prostaglandin F2 alpha.

The present study has demonstrated: (1) glibenclamide can reduce resting tension in canine cerebral arteries but has no effect on resting tension in the rat aorta; (2) glibenclamide can relax prostaglandin F2 alpha-induced contractions in the rat aorta, and in canine femoral, mesenteric, renal, coronary, basilar and middle cerebral arteries; (3) the relaxation produced by glibenclamide in rat aorta is comparable to that of glyceryl trinitrate and stronger than that of papaverine; (4) canine femoral arteries are less sensitive to glibenclamide than the other arteries; (5) in cerebral arteries glibenclamide was as effective as papaverine, but less effective than glyceryl trinitrate; (6) the actions of glibenclamide on cerebral arteries are not mediated by cGMP as they were not blocked by methylene blue, an inhibitor of guanylate cyclase; (7) the effects of glibenclamide are not endothelium-dependent. The mechanism by which glibenclamide produces relaxation is not clear; while the drug is known to block ATP-dependent potassium channels, in vascular smooth muscle this would cause contraction, not dilation. The action of glibenclamide may be at the level of the receptor or the signal transduction process.

Animals↗
PubMed1991

Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.

Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.

Animals↗
PubMed1990

Excitability changes in the crustacean motor axons following activity.

It has been shown experimentally that the crustacean motor axon is supernormally excitable following a train of action potentials (Zucker 1974). Such a phenomenon can lead to recruitment of terminals which are unexcited at low rates of stimulation. Although currents underlying the crustacean motor axon have been characterized (Connor et al. 1977), it is not known whether this membrane model accounts for a supernormal period, what might cause superexcitability in this model, or how excitability might change during repetitive stimulation. In present study, it is demonstrated that the crustacean motor axon model does predict a supernormal period, that the supernormal period results from slow recovery from inactivation of the transient potassium, or A, current, and that supernormal excitability is enhanced by repetitive stimulation.

Action Potentials↗
PubMed1989

Theoretical response of a bifurcating axon with a locally altered axial resistivity.

A short region of high axial resistivity at one daughter branch of an axonal bifurcation can produce frequency dependent differential conduction of action potentials. The increase in resistivity need be only a few times that in the rest of the axon and length of the affected region need be only a fraction of a resting length constant (based on the local value of axial resistivity). The typical pattern observed will be that the unaffected daughter branch will conduct action potentials from the parent axon normally at all frequencies of stimulation, but the branch with the high resistance region will only follow action potentials within a restricted frequency range. In that band-pass region, the branch may conduct nearly all or only a small percentage of the action potentials from the parent axon.

Action Potentials↗
PubMed1989

Solution of the Hodgkin-Huxley and cable equations on an array processor.

This paper presents a method for the solution of equations for membrane ionic currents and the cable equation which describes the interaction of various segments in a compartmentalized model of the neuron. The method embodies some innovations which would speed calculation of propagating action potentials in any computing environment, but were specifically designed to permit the use of a relatively inexpensive array processor. The array processor produces an improvement in speed of calculation which permits exploration of a wider range of neuronal phenomena than has been previously feasible.

Action Potentials↗
PubMed1988

Properties of synaptic transmission at the neuromuscular junction of the squid, Loligo opalescens.

1. Spontaneous and evoked synaptic activity were recorded from the muscles of squid fin and mantle. These spontaneous synaptic potentials were large (up to 30 mV) and pleomorphic. Their amplitudes were not normally distributed, nor did they appear to be clustered in integral multiples of some "unit" event size. 2. Electrical stimulation of the nerve resulted in muscle twitches when the bath calcium concentration was a third normal or higher. The frequency of spontaneous synaptic events was unaffected by low calcium. 3. The large size of spontaneous events may mean that the synchronized release of only a few such "quanta" are sufficient to cause muscle action potentials and contraction. 4. The shapes of spontaneous events correlated poorly with their amplitudes, which is consistent with release from multiple synaptic sites with distinct properties.

Animals↗
PubMed1987

Cholinergic transmission at newly formed synapses made by retinal neurons in culture.

The purpose of this study was to investigate the properties of cholinergic transmission at nascent synapses formed by neurons from the embryonic chick retina. By using a cell culture system in which striated muscle cells served as postsynaptic targets for dissociated retinal neurons, it was possible to record synaptic activity soon after the establishment of a functional cholinergic synapse. Postsynaptic potentials ranged from a few hundred microvolts to greater than 10 mV. The high temperature dependence (Q10 of 10) of this cholinergic transmission indicated that the release of acetylcholine from the embryonic retinal neurons was not injury-related. The wide range in event amplitudes did not appear to be due to electrotonic conduction from adjacent myotubes. Rather, a lack of correlation between event amplitude and rise time indicated that the release of acetylcholine occurred over a confined area of contact. Amplitude histograms of these events always showed a unimodal distribution, with small events being most common. No pattern to the timing of the events was evident. In addition, the inward current blockers, tetrodotoxin and cadmium did not affect this activity. Taken together, our findings indicate that the embryonic retinal neurons studied in this culture system spontaneously release acetylcholine in a pulsatile manner by a mechanism that is stimulus-independent and highly temperature sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1978

A numerical method to model excitable cells.

We have extended a fast, stable, and accurate method for the numerical solution of cable equations to include changes in geometry and membrane properties in order to model a single excitable cell realistically. In addition, by including the provision that the radius may be a function of distance along an axis, we have achieved a general and powerful method for simulating a cell with any number of branched processes, any or all of which may be nonuniform in diameter, and with no restriction on the branching pattern.

Action Potentials↗