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K J Long

Publications and source records attributed to K J Long.

At least 19 recordsLinked to original sources
PubMed1996

Stimulatory regulation of the large-conductance, calcium-activated potassium channel by G proteins in bovine adrenal chromaffin cells.

G proteins regulate the electrical activity of various cells through their actions on membrane ion channels. In the present study, the effect of G proteins was examined on unitary, large conductance (BK), Ca(2+)-activated K+ channels measured in excised, inside-out patches of membrane obtained from cultured bovine adrenal chromaffin cells. Cytoplasmic application of either guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or AlF-4 to stimulate G proteins resulted in a > 4-fold increase in the open probability of the BK channel measured at +40 mV in the presence of a 1 microM concentration of Ca2+. A similar stimulatory regulation was observed after the addition of an activated, mixed Gi/Go alpha preparation. The increase in the open probability during G protein stimulation was associated with a large reduction in the duration of a long closed state of the channel and could be observed in the presence of a protein kinase inhibitor. The half-maximal voltage required for steady state activation of the BK channel decreased from +63 mV to +48 mV in the presence of GTP gamma S. In addition, the half-maximal Ca2+ concentration required for channel opening was reduced from 11.7 microM in control measurements to 1.3 microM during regulation by GTP gamma S. Thus, G proteins increase the open probability of the chromaffin BK Ca(2+)-activated K+ channel by shifting the voltage dependence of channel gating to more negative potentials and by enhancing the affinity of the channel for Ca2+. Stimulatory regulation may provide a compensatory mechanism for decreasing the action potential duration during secretagogue-mediated exocytosis.

Adrenal Medulla↗
PubMed1994

A calcium-activated potassium channel in growth plate chondrocytes: regulation by protein kinase A.

Single channel K+ currents were recorded from inside-out patches of membrane obtained from cultured chicken growth plate chondrocytes. With a symmetrical 140 mM concentration of K+ across the cell membrane, a large conductance (211 pS), outward-rectifying, K+ channel was identified. Opening of this channel was dependent on the presence of internal Ca2+ with half maximal activation of the channel occurring with 3 microM Ca2+. The channel was blocked by internal application of tetraethylammonium (IC50 = 45 mM) and 1 mM Ba2+. Application of the catalytic subunit of protein kinase A to the cytosolic membrane resulted in over a three-fold increase in the open probability for the channel. Thus, growth plate chondrocytes contain a large-conductance, Ca(2+)-activated K+ channel which can be up-regulated during stimulation of protein kinase A.

Adenosine Triphosphate↗
PubMed1994

Properties of a protein kinase C-activated chloride current in guinea pig ventricular myocytes.

Cardiac ventricular myocytes from several species, including the guinea pig, possess a cAMP-dependent protein kinase A (PKA)-activated Cl- channel. In the present study, the properties of a protein kinase C (PKC)-activated Cl- current were studied in isolated guinea pig ventricular myocytes using the whole-cell arrangement of the patch-clamp technique. Intracellular dialysis of ventricular cells with PKC resulted in the activation of a large background current that displayed time-independent kinetics. In the presence of 146 mmol/L external Cl- and 71 mmol/L internal Cl-, the reversal potential (Erev) of the background current (-17 +/- 1 mV) was close to that of the Cl- equilibrium potential (-18 mV), and the current versus voltage relation for the current was outward rectifying in shape. When [Cl-]i or [Cl-]o was reduced by substitution of Cl- with aspartic acid, Erev for the background current shifted in a manner expected for a Cl(-)-selective channel. Based on Erev measurements, the permeability sequence for this PKC-activated Cl- channel was determined to be SCN- > I- > Br- congruent to Cl-. The PKC-activated Cl- current was not inhibited by the Cl- channel blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (100 mumol/L) but could be blocked by anthracene-9-carboxylic acid (1 mmol/L). Activation of the current was abolished in the presence of the PKC inhibitor staurosporine (2.5 mumol/L). Under conditions designed to cause a maximal activation of the Cl- channels by PKC, the addition of forskolin (1 mumol/L) to stimulate PKA caused only a slight further increase in the amplitude of the Cl- current. Thus, PKC activates a Cl- channel in guinea pig ventricular cells with properties similar but not identical to the PKA-activated channel.

Animals↗
PubMed1993

Clinical evaluation of romifidine/ketamine/halothane anaesthesia in horses.

Romifidine, 100 micrograms/kg administered by intravenous injection, was evaluated as a premedicant to ketamine/halothane anaesthesia in 60 horses. Sedation developed within one to two minutes. In three cases mild staggering occurred within two minutes. Anaesthesia was induced after five minutes by the intravenous administration of ketamine (2 to 2.2 mg/kg). A mean time of 79 seconds elapsed before lateral recumbency was adopted. Fifty-four of the horses sank smoothly to the floor, with occasional steps sideways. Jaw tone, limb rigidity and mild muscle tremors often persisted for short periods after induction. Complete relaxation was achieved on average two minutes after the administration of ketamine. The transition to oxygen/halothane anaesthesia was excellent or good in 53 cases. The mean duration of anaesthesia was 79 minutes. Forty-seven of the horses were able to stand after one or two attempts with little or no ataxia. After halothane administration ceased, the mean time to sternal recumbency was 25 minutes and the mean time to standing was 33 minutes. Most horses appeared to be sedated upon standing, but they were able to walk soon after regaining their feet. The characteristics of the induction of anaesthesia were similar to those seen when detomidine/ketamine or xylazine/ketamine are used. The maintenance of anaesthesia with halothane was similar to that following other induction protocols, and the recovery from anaesthesia was smooth and free from excitement.

Anesthesia↗
PubMed1993

Formaldehyde-induced airway hyperreactivity in vivo and ex vivo in guinea pigs.

Human exposure to formaldehyde is extensive, in both the indoor and the outdoor environment. The airways are clearly an important site of action of formaldehyde. Although many previous studies have examined the effect of formaldehyde in the upper respiratory tract, it remains controversial whether this compound can affect the lower respiratory tract. To determine whether formaldehyde induces airway hyperreactivity, guinea pigs were exposed to formaldehyde or filtered air (sham control) for 2 or 8 hr. Airway smooth muscle responsiveness was evaluated in vivo and ex vivo. Specific pulmonary resistance and airway reactivity (to infused acetylcholine) increased with formaldehyde exposure. Formaldehyde exposure caused bronchoconstriction and hyperreactivity at lower concentrations when exposure duration was extended from 2 to 8 hr. Exposure to > or = 0.3 ppm formaldehyde for 8 hr was sufficient to produce a significant increase in airway reactivity, while similar effects only occurred after > 9 ppm formaldehyde for 2 hr. Formaldehyde exposure also heightens airway smooth muscle responsiveness to acetylcholine (or carbachol) ex vivo. These effects occurred with no evidence of epithelial damage or inflammation up to 4 days after formaldehyde exposure. Thus, at concentrations relevant to environmental exposure, formaldehyde, a common indoor air pollutant, alters airway smooth muscle reactivity in guinea pigs. These findings suggest that the duration of exposure is important to the induction of airway hyperreactivity and that prolonged, low-level exposures may generate abnormal physiological responses in the airways not detectable after acute exposures.

Animals↗
PubMed1992

Acute eosinophilic interstitial pulmonary disease in a pony.

An outdoor pony which developed severe respiratory distress in February was shown to have acute interstitial pulmonary disease (alveolitis), which was characterised by a massive exudation of eosinophil rich fluid into the airways. While antibiotic treatment before referral was ineffective, the condition rapidly responded to corticosteroid therapy. No evidence of lungworm was present and it appears that this interstitial pulmonary disease had an immune-mediated aetiology. Bronchoalveolar lavage cytology was of great value in the diagnosis and monitoring of this case.

Adrenal Cortex Hormones↗
PubMed1992

Inhibition of heart calcium and chloride currents by sodium iodide. Specific attenuation in cAMP-dependent protein kinase-mediated regulation.

The enzymes cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) regulate the activity of cardiac ion channel proteins. In this study the whole-cell arrangement of the patch clamp technique was used to examine the effect of NaI on PKA-stimulated Cl- and Ca2+ channels in isolated guinea pig ventricular myocytes. Cl- currents (ICl) activated either by the beta-adrenergic agonist isoproterenol or the membrane-soluble cAMP analogue, 8-chlorphenylthio (8-CPT) cAMP, were greatly reduced in amplitude after substitution of an external solution containing 140 mM NaCl with a solution containing 140 mM NaI. This reduction was accompanied by a shift of -7 mV in the reversal potential (Erev) for ICl and could be reversed upon return to the NaCl external solution. Inhibition of ICl by NaI occurred in a concentration-dependent manner and was more pronounced for inward ICl (IC50 = 19 mM at -60 mV) than for outward ICl (IC50 = 60 mM at +60 mV). In contrast to ICl activated by PKA, ICl activated by PKC was slightly augmented in the presence of NaI and the Erev was found to shift by -15 mV. Based on these data, the relative permeability of I- to Cl- (PI/PCl) for this channel was calculated to be 1.79. NaI produced no change in the amplitude of inward calcium currents (ICa) recorded under basal conditions, but strongly inhibited ICa augmented by isoproterenol and 8-CPT cAMP, and during dialysis of cells with the catalytic subunit of PKA (CS). The in vitro incorporation of [gamma-32P]ATP into histone IIA and Kemptide, measured in the presence of PKA and cAMP, was not significantly different in assay mixtures containing salts of Cl- and I-. However, the ability of isoproterenol to augment basal ICa in whole-cell experiments was attenuated when experiments were carried out entirely in NaI external solution. Thus, the reduction in ICl and ICa observed in this study may result from a direct effect of I- on the phosphorylation/dephosphorylation of cardiac ion channel proteins or associated regulatory proteins.

Adenosine Triphosphate↗
PubMed1992

Standardised imaging technique for guided M-mode and Doppler echocardiography in the horse.

Eighteen echocardiographic images useful for diagnostic imaging, M-mode echocardiography, and Doppler echocardiography of the equine heart were standardised by relating the position of the axial beam to various intracardiac landmarks. The transducer orientation required for each image was recorded in 14 adult horses by describing the degree of sector rotation and the orientation of the axial beam relative to the thorax. Repeatable images could be obtained within narrow limits of angulation and rotation for 14 of the 18 standardised images evaluated. Twenty-seven National Hunt horses were subsequently examined using this standardised technique. Selected cardiac dimensions were measured from two-dimensional and guided M-mode studies. Satisfactory results were achieved in 26 of the 27 horses. There was no linear correlation between any of the measured cardiac values and bodyweight. There was no significant difference between measurements taken from the left and the right hemithorax. Six horses were imaged on three consecutive days to assess the repeatability of the measurements. No significant difference was found between measurements obtained on different days. This study demonstrates a method for standardised echocardiographic evaluation of the equine heart that is repeatable, valuable for teaching techniques of equine echocardiography, applicable for diagnostic imaging and quantification of cardiac size, and useful for the evaluation of blood-flow patterns by Doppler ultrasound.

Animals↗
PubMed1986

Infection as a possible etiology of hypsarrhythmia.

In 480 patients with hypsarrhythmia (H) and also in a matched control group (180), evidence for some recent infection was determined as a possible etiology for the H. Evidence for infection was found in 38% of the H patients, significantly (p less than 0.0005) different from the 23% in the control group. Although the H group more often showed specific infections with a known organism, a greater difference was seen in nonspecific infections with temperatures of at least 103 degrees F. These data provide further evidence that infectious disease has likely played a more significant role in H than has been previously appreciated.

Communicable Diseases↗
PubMed1985

No-show behavior.

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Appointments and Schedules↗
PubMed1981

Growth hormone stimulation of lipolysis and cyclic AMP levels in perifused fat cells.

A rapid, sustained lipolytic response to growth hormone (GH; 20 microgram/ml) was observed in experiments using the perifused fat cell system. No lipolytic response to this agent was observed when fat cells were incubated by the traditional flask incubation method, although isoproterenol stimulated lipolysis in this preparation. In experiments using flask incubated fat cells, isoproterenol increased cyclic AMP content while GH had no effect. However, in the presence of theophylline, isoproterenol and GH significantly increased cyclic AMP levels. In perifused fat cells, both isoproterenol and GH significantly increased cyclic AMP levels in the absence of theophylline. The presence of adenosine deaminase resulted in significant increases in the lipolytic response to isoproterenol and unmasked a lipolytic response to GH when the flask-incubated fat cell system was used. The antilipolytic action of adenosine was determined in perifused fat cells. It was found that the lipolytic response to GH was at least 10 times as sensitive to the inhibitory action of adenosine as was the lipolytic response to isoproterenol. It is concluded that the lipolytic response to GH in the flask-incubation method is prevented by the accumulation of adenosine. This rapid lipolytic response is unmasked in the perifused fat cell system because adenosine fails to accumulate as it is washed from the cell population by the constantly flowing buffer.

Adenosine↗