The content of Na, K and Cl and the extracellular space were measured in isolated strips of smooth muscle from the bovine trachea, in normal physiological solution and in the presence of histamine (65 μmol/l). Histamine produced small increases in cell content of Na and K, and a large decrease in Cl. Histamine also produced a large increase in the measured rate of efflux of radioactive Cl, but only small changes in the effluxes of tracer Na and K. It is suggested that the depolarization of the cell membrane caused by histamine is the result of an increase in the membrane’s permeability to chloride ions.

SUMMARY1. 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.2. 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.3. Atropine blocked both components of the biphasic response to exogenous acetylcholine.4. Tetrodotoxin blocked neither phase of the response to exogenous acetylcholine even though a similar biphasic response to electrical stimulation was severely disrupted.5. Application of exogenous substance P produced a biphasic response of similar magnitude and form to that produced by acetylcholine.6. 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.7. It is concluded that the inhibitory component of the biphasic response to exogenous acetylcholine occurs as a non‐specific sequel to contraction.

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.

The fine structure of the bovine trachealis muscle has been described. Muscle bundles were followed for some distance by serial sectioning and it can be shown that major changes in bundle architecture occur with rapidity. Extracellular space was 39.7% of tissue volume, measured optically, and 51.6% measured isotopically. The packing densities of the cells of the trachealis were estimated. Muscle cell length is 806 μm, volume is 2950 μm3, volume-to-surface area ratio is 0.40, and surface area is 7375 μm2. If the membrane area of the caveolae intracellulares is included, the volume to surface area ratio becomes 0.21. The spatial distribution of nexuses was examined. There are 145 nexuses/cell occupying 21.75 μm2 membrane/cell. The percentage cell volume occupied by the major organelles was estimated and their interrelationships examined. Sarcoplasmic reticulum occupies 1.94% of cell volume; less than would be predicted by current models of smooth muscle behavior.

cardiac failure. Atrial fibrillation was present, but there was no cardiac enlargement and no murmurs. Chest radiography confirmed that the cardiac contour and size and lung fields were normal. Echocardiography showed no abnormality of either the mitral or aortic valve. Cardiac enzyme activities, electrolyte concentrations, and full blood count were all normal, and glandular fever screening test was negative. Complement fixation tests were negative for Coxiella burneti, Myocoplasma pneumoniae, influenza A and B, adenovirus, parainfluenza, herpes simplex, respiratory syncytial virus, and cytomegalovirus. Titres for psittacosis, however, were as follows: 8 on 22 December 80, 512 on 14 January 81, 512 on 18 February 81, 64 on 16 April 81, and 32 on 17 June 81. Treatment with tetracycline was started and continued for two months. By late January 1981 his symptoms had disappeared and when the titre to chlamydia B had fallen in May 1981 he was admitted to hospital for cardioversion because of persistence of atrial fibrillation. After successful cardioversion electrocardiography showed no evidence of pulmonary mitrale, ventricular hypertrophy, or myocardial ischaemia. Ten days later, after a mild flu-like illness, the heart lapsed into atrial fibrillation again despite maintenance quinidine treatment. Repeat cardioversion was not required as sinus rhythm occurred spontaneously after several days. Closer questioning failed to elicit any exposure to or contact with birds by the patient or any member of the family.

Mechanisms of the histamine-induced inhibitory response (the H2-response) in neurons of the marine mollusc Onchidium, were further investigated following the preceding paper. The H2-response in normal saline was blocked by ouabain, but the response recovered after a short exposure to Na-free solution containing ouabain. The recovery was only transient in the continuous presence of ouabain. When external Na was reduced to about18 normal concentration (60 mM), the H2-response became sensitive to removal of external Ca, but insensitive to ouabain. The suppressing effect of Ca removal and the recovery by Ca readmission appeared very slowly. However, in about13 normal Na concentration (150 mM) the H2-response was suppressed by removal of Ca, only in the presence of ouabain. The Na-gradient may be regulated by the ouabain-insensitive transport, such as a NaCa exchange in addition to the ouabain-sensitive Na-pump. The NaCa exchange probaly dominates over the ouabain-sensitive Na-pump only when passive Na-influx is reduced in a low external Na concentration. The H2-response was markedly inhibited by DNP (5 × 10−4 M) and cyanide (2 × 10−3 M), while the hyperpolarization produced by glutamate, which was accompanied by a large reduction of membrane resistance, was not affected by these metabolic inhibitors. Over a wide range of external Na concentrations, the membrane potential was lower in the presence than in the absence of external Ca. This may be explained by the hypothesis that there is an electrogenic NaCa exchange in which Ca-influx is coupled with Na-efflux. According to a similar hypothesis, the H2-response is produced by the transport system in which Ca-efflux is coupled with Na-influx and the system is controlled by the transmembrane Na gradient.

Histamine elicited depolarization (excitation) in some neurons and hyperpolarization (inhibition) in other neurons of the central nervous system of the marine mollusc,Onchidium verruculatum. The histamine sensitive region was along the axon at some distance from the soma. H1-receptor blockers (SA-97 and mepyramine) suppressed the excitatory (H1) response without affecting the inhibitory (H2) response, while H2-receptor blockers (burimamide and metiamide) suppressed the H2-response without affecting the H1-response. The H1-response was associated with a marked increase in membrane conductance and was blocked by removal of the external Na. The H2-response consisted of a hyperpolarization without much change in conductance, compared with the hyperpolarization of same amplitude produced by glutamate in the same neuron. Passive polarization of the membrane and reduction of Cl concentrations to15−125 caused to significant change in H2-response. The H2-response was slightly suppressed in K-free saline. Thus, it seems difficult to account for the hyperpolarization only by an increase in K or Cl conductance. Complete removal of Na and addition of ouabain blocked the H2-response, suggesting a contribution of an electrogenic Na-pump to the hyperpolarization. However, in 20 mM Na saline with or without K, histamine still caused clear hyperpolarization. In this solution, the histamine response was not affected by ouabain. Although it is difficult to exclude the possibility that an increase in K conductance may be responsible for the hyperpolarization, it is tentatively proposed as a hypothesis that the H2-response involved some active transport mechanism, different from a ouabain-sensitive electrogenic Na-pump.