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C T Kirkpatrick

Publications and source records attributed to C T Kirkpatrick.

26 records · Page 2Linked to original sources

Excitation and contraction in bovine tracheal smooth muscle.

1. The smooth muscle layer of the bovine trachea was studied in vitro with the micro-electrode and sucrose-gap techniques. The membrane potential was stable at--47-6 plus or minus 0-98 (S.E. of mean) mV, and there was no spontaneous electrical or mechanical activity. 2. The cell membrane had strong rectifying properties, making it impossible to elicit action potentials by electrical stimulation in normal Krebs Solution. The rectification was abolished by TEA (30 mmol/l), which depolarized the membrane and produced plateau-type action potentials. 3. The spontaneous repetitive action potentials produced by TEA were associated with rhythmic oscillatory contractions of the muscle strips. 4. Histamine caused an increased tone, with superimposed rhythmic fluctuations in tension. The electrical response consisted of depolarization, with rhythmic slow oscillations in potential (slow waves) which were synchronous with the fluctuations in tension. 5. Acetylcholine produced smooth, tonic contractures of tracheal muscle strips, and caused simple depolarization of the membrane. No action potentials were recorded. 6. In calcium-free solutions containing EGTA, the mechanical response to TEA was completely abolished; the response to histamine was greatly reduced; the response to acetylcholine was reduced to a lesser extent. All responses reverted to normal when normal concentrations of extracellular calcium were restored. 7. Lanthanum added to the bathing solution abolished the contraction due to TEA even though the solution contained calcium. It reduced the histamine-induced contraction to 26% of control, and reduced the acetylcholine-induced contraction to 58% of control; extracellular calcium was present throughout. 8. It is suggested that TEA produces contraction by promoting influx of calcium ions into the cytoplasm. Acetylcholine, and to a smaller extent histamine, are less dependent upon the presence of extracellular calcium, and may be capable of releasing calcium sequestered within the cell; acetylcholine appears to be more effective in releasing sequestered calcium.

Acetylcholine↗

Interaction between drugs and potassium-rich solutions in producing contraction in bovine tracheal smooth muscle: studies in normal and calcium-depleted tissues.

1. The contracture normally induced in isolated bovine tracheal smooth muscle by potassium-rich solution was abolished by removal of the extracellular calcium. The contraction returned when calcium was added to the solution in a concentration greater than 0.05 mmol/l. 2. The amplitudes of the potassium-contracture, and of the contractile responses to histamine and acetylcholine in normal physiological solutions, declined at low temperatures (15-25 degrees C). If drugs were added during the plateau phase of the potassium contracture, the extra tension developed above the contracture did not change with temperature. 3. Calcium-depletion reduced the responses to drugs, and repeated application of the drugs in calcium-free solution produced progressively smaller contractions, suggesting that an intracellular store of calcium was being used up. 4. Depolarization of calcium-depleted tracheal muscle by high-K+ solution without calcium produced responses to drugs which were larger than those in sodium-based calcium-free solutions. There was no potentiation in a solution in which sodium was replaced by sucrose, suggesting that potassium was not acting simply by replacing the sodium. 5. It is suggested that depolarization of the membrane by potassium makes available a fraction of bound calcium which was not available in calcium-free sodium-based solution.

Acetylcholine↗

The contractile response of smooth muscle to immersion in hypertonic solutions.

1. Strips of bovine tracheal muscle and rabbit aorta produced sustained contractions on perfusion with Krebs solution made twice normal strength by addition of sucrose. The contractures were relaxed on return to normal Krebs solution. 2. Similar contractures were produced by tracheal muscle strips in Krebs solutions made twice normal strength by addition of galactose, glucose or NaCl whereas urea caused only a transient contraction. 3. In twice normal strength Krebs solution (sucrose added) the basal tension of rat portal vein and guinea-pig taenia coli was increased. Spontaneous mechanical activity was maintained, but the frequency of contractions was reduced. 4. The hypertonic contracture of bovine trachea in twice normal strength Krebs solution (sucrose added) was reduced by 15% by omission of Ca from the bathing fluid (0.1 mmol/l EGTA added). Severe Ca depletion, by prolonged washing in Ca-free Krebs with 12.5 mmol/l EGTA and Carbachol added, resulted in a 77% reduction in the hypertonic contracture. 5. In twice normal Krebs solution (sucrose added), the hypertonic contracture was partially relaxed by isoprenaline (4 x 10(-6) mol/l); the contractile response to carbachol was reduced; the contractile response to high-K Krebs solution was maintained. 6. Atropine (5 x 10(-7) mol/l) abolished the contractile response to carbachol, but had no effect on the hypertonic contracture. 7. It is suggested that the contraction of bovine tracheal strips in hypertonic solutions is mainly due to activation of the contractile myofilaments rather than simple cell shrinkage. Hypertonic solutions may also interfere with some steps in the excitation-contraction coupling sequence.

Animals↗

Contractures produced by carbamate anticholinesterases in bovine tracheal smooth muscle.

1. In isolated strips of bovine tracheal muscle the carbamate anticholinesterases, neostigmine and eserine caused similar, slowly-developing, sustained spasms which were concentration-related in the range 10(-7)-10(-4) mol/l; these spasms could be abolished either by withdrawing the anticholinesterase or by addition of atropine (5 X 10(-7) mol/l). 2. Depletion of tissue stores of acetylcholine using hemicholinium-3 with or without electrical stimulation rendered the muscle unresponsive to neostigmine (10(-6) mol/l). Responses to acetylcholine itself were not impaired. 3. A low concentration of neostigmine (10(-8) mol/l) did not cause spasm but enhanced the contractile response of bovine trachealis to acetylcholine, carbachol and histamine. This concentration of neostigmine also increased the muscle's contraction upon exposure to a high-potassium solution, even in the presence of atropine (5 X 10(-7) mol/l). 4. It is concluded that neostigmine and eserine cause spasm not only by preventing breakdown of endogenously released acetylcholine but also by stimulating release of acetylcholine from nerve terminals and by a non-specific enhancement of muscle contraction.

Acetylcholine↗

Relaxation following contraction in tonically contracted smooth muscle from the bovine trachea.

Isometric tension was recorded from strips of bovine tracheal smooth muscle in which the tone had been artificially raised by agonist drugs such as histamine and carbachol. Application of exogenous acetylcholine produced a biphasic response consisting of an initial contraction followed by a more prolonged relaxation before tone was restored to normal. Atropine blocked both components of the biphasic response to exogenous acetylcholine. Tetrodotoxin blocked neither phase of the response to exogenous acetylcholine even though a similar biphasic response to electrical stimulation was severely disrupted. Application of exogenous substance P produced a biphasic response of similar magnitude and form to that produced by acetylcholine. Application of exogenous histamine (tone raised by carbachol) also produced a biphasic response although higher concentrations were required to produce a relaxation of equal magnitude to that produced by acetylcholine. It is concluded that the inhibitory component of the biphasic response to exogenous acetylcholine occurs as a non-specific sequel to contraction.

Acetylcholine↗