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Biomedical subjects

J E Kelly

Publications and source records attributed to J E Kelly.

12 recordsLinked to original sources
PubMed1996

Characteristics of cocaine block of purified cardiac sarcoplasmic reticulum calcium release channels.

We have examined the effects of cocaine on the SR Ca2+ release channel purified from canine cardiac muscle. Cocaine induced a flicker block of the channel from the cytoplasmic side, which resulted in an apparent reduction in the single-channel current amplitude without a marked reduction in the single-channel open probability. This block was evident only at positive holding potentials. Analysis of the block revealed that cocaine binds to a single site with an effective valence of 0.93 and an apparent dissociation constant at 0 mV (Kd(0)) of 38 mM. The kinetics of cocaine block were analyzed by amplitude distribution analysis and showed that the voltage and concentration dependence lay exclusively in the blocking reaction, whereas the unblocking reaction was independent of both voltage and concentration. Modification of the channel by ryanodine dramatically attenuated the voltage and concentration dependence of the on rates of cocaine block while diminishing the off rates to a lesser extent. In addition, ryanodine modification changed the effective valence of cocaine block to 0.52 and the Kd(0) to 110 mM, suggesting that modification of the channel results in an alteration in the binding site and its affinity for cocaine. These results suggest that cocaine block of the SR Ca2+ release channel is due to the binding at a single site within the channel pore and that modification of the channel by ryanodine leads to profound changes in the kinetics of cocaine block.

Animals↗
PubMed1993

Modification of cardiac Na+ channels by anthopleurin-A: effects on gating and kinetics.

We used the whole cell patch clamp technique to investigate the characteristics of modification of cardiac Na+ channel gating by the sea anemone polypeptide toxin anthopleurin-A (AP-A). Guinea pig ventricular myocytes were isolated enzymatically using a retrograde perfusion apparatus. Holding potential was -140 mV and test potentials ranged from -100 to +40 mV (pulse duration 100 or 1000 ms). AP-A (50-100 nM) markedly slowed the rate of decay of Na+ current (INa) and increased peak INa conductance (gNa) by 38 +/- 5.5% (mean +/- SEM, P < 0.001, n = 12) with little change in slope factor (n = 12) or voltage midpoint of the gNa/V relationship after correction for spontaneous shifts. The voltage dependence of steady-state INa availability (h infinity) demonstrated an increase in slope factor from 5.9 +/- 0.8 mV in control to 8.0 +/- 0.7 mV after modification by AP-A (P < 0.01, n = 14) whereas any shift in the voltage midpoint of this relationship could be accounted for by a spontaneous time-dependent shift. AP-A-modified INa showed a use-dependent decrease in peak current amplitude (interpulse interval 500 ms) when pulse duration was 100 ms (-15 +/- 2%, P < 0.01, n = 17) but showed no decline when pulse duration was 100 ms (-3 +/- 1%). This use-dependent effect was probably the result of a decrease in the recovery from inactivation caused by AP-A which had a small effect on the fast time constant of recovery (from 4.1 +/- 0.3 ms in control to 6.0 +/- 1.1 ms after AP-A, P < 0.05) but increased the slow time constant from 66.2 +/- 6.5 ms in control to 188.9 +/- 36.4 ms (P < 0.002, n = 19) after exposure to AP-A. Increasing external divalent cation concentration (either Ca2+ or Mg2+) to 10 mM abolished the effects of AP-A on the rate of INa decay. These results demonstrate that modification of cardiac Na+ channels by AP-A markedly slowed INa inactivation and altered the voltage dependence of activation; these alterations in gating characteristics, in turn, caused an increase in gNa presumably by increasing the number of channels open at peak INa. AP-A slows the rate of recovery of INa from inactivation which is probably the basis for a use-dependent decrease in peak amplitude. Finally, AP-A binding is sensitive to external divalent cation concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Lipoid proteinosis: Urbach-Wiethe disease.

An otherwise healthy patient with Urbach-Wiethe disease required surgical removal of two 3rd molar teeth. In this multisystem disorder infiltration of the buccal, pharyngeal and laryngeal mucosa may cause difficulties with tracheal intubation and increase the likelihood of trauma. The anaesthetic implications and management are described.

Adult↗
PubMed1986

Inputs to the pontine A5 noradrenergic cell group: a horseradish peroxidase study.

The noradrenergic A5 cell group of the caudal ventrolateral pons has been implicated in regulation of cardiovascular activity. The efferent fibers from this cell group have been established, but the sources of afferents into the region have not. Horseradish peroxidase (HRP) was injected into the A5 region in rabbits, or into regions surrounding A5. The pattern of retrograde labeling indicated that several areas known to have a role in the control of cardiovascular function by the brain send projections to and/or through the A5 region.

Adrenergic Fibers↗
PubMed1982

Temperature elevations in orthopaedic cutting operations.

Temperature measurements were made in bovine cortical bone using two cutting burst at 20,000 and 100,000 rpm and two reciprocating saw blades at 20,000 strokes per minute. A combination of feed rates and depths of cuts were investigated for the cutting burs. Cortical temperatures decreased as a result of increases in feed rate, but increased as the depth of cut increased. Temperature increase due to an increase in rotational speed was dependent upon the particular bur. The cutting forces were observed to increase with feed rate and depth of cut, but to decrease with increased rotational speed. The effect of saw design and irrigation had a significant effect on the cortical temperature. Without irrigation, the bone temperature exceeded temperatures reported to produce thermal necrosis. Clinical tests during total joint replacement indicated saw temperatures exceeding 200 degrees C when irrigation was not used.

Animals↗