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R D Purves

Publications and source records attributed to R D Purves.

48 records · Page 3Linked to original sources

Muscarinic excitation: a microelectrophoretic study on cultured smooth muscle cells.

1 Acetylcholine was applied iontophoretically to smooth muscle cells cultured from taeniae coli of new-born guinea-pigs. Responses were recorded with intracellular microelectrodes.2 Acetylcholine induced depolarization, spike generation and contraction. Large conductance increases could be measured during the action of acetylcholine.3 Injection of depolarizing currents through the recording electrode reversed the sign of potential responses. The reversal potential was -5 to -25 mV.4 Minimum latencies of responses to acetylcholine were 120-500 ms. These values were not attributable to diffusion time.5 Attention is drawn to the long latencies of a variety of muscarinic responses, and the suggestion made that muscarinic mechanisms as a class may be characterized by a long activation time.

Acetylcholine↗

Observations on 'fade': a complication of the contractile response of smooth muscle to a large dose of an agonist.

1. A study has been made of the time course of contraction of guinea-pig isolated ileum when suddenly exposed to a high concentration of acetylcholine, carbachol or histamine. With a sufficiently large dose there was a ;fading' of the abrupt initial contraction. A sustained contraction followed, provided that the agonist was not washed out of the organ bath.2. The fade produced by giving large equipotent doses of acetylcholine and histamine simultaneously was substantially greater than that obtained by giving either agonist alone. It was comparable to that produced by a double dose of acetylcholine or histamine. This result does not support any explanation of fade based on receptor occupancy.3. The extent of fade and the level of the sustained contraction were strongly affected by the calcium concentration of the bath fluid: the higher the calcium concentration the less was the fade. It is suggested that fade occurs when there is such intense stimulation of receptors that excitation-contraction coupling becomes temporarily less efficient due to depletion of calcium from a store.

Acetylcholine↗

Intracellular recordings from ganglia of the thoracic sympathetic chain of the guinea-pig.

1. Intracellular recordings have been obtained from cells of thoracic paravertebral sympathetic ganglia of guinea-pigs.2. Resting potentials were 50-70 mV. The steady-state current-voltage curve was linear for all hyperpolarizations and usually for depolarizations up to 10 mV. The slope of this curve was 19-186 MOmega (mean 55 MOmega). Time constants of cells were 6-14 msec (mean 9.1 msec).3. Most cells maintained a high rate of firing of action potentials during strong current pulses.4. Indirect stimulation via the rami communicantes or the interganglionic nerves of the sympathetic chain evoked a graded synaptic response which could lead to the discharge of one or more action potentials. Hexamethonium blocked the responses to such stimulation. Occasionally an all-or-none response remained, apparently conducted antidromically along the cell's axon.5. Spontaneous synaptic potentials were observed. Their occurrence frequency was increased during indirect stimulation. If they are assumed to represent single quanta of release of transmitter, the quantal content of a threshold synaptic potential was 8-20 quanta.6. Preganglionic fibres could ascend at least three segments or descend two after entering the sympathetic chain. They had conduction velocities of 0.1-1.1 m/sec.7. Inexcitable cells were frequently impaled. Repetitive indirect stimulation gave rise in these cells to a large (20 mV) slow depolarizing response.

Action Potentials↗

Formation of the aqueous humor.

1. Glaucoma is a worldwide disease affecting approximately 1-2% of the population aged over 35 years in industrial countries and is a major cause of blindness. 2. Glaucoma is usually associated with an increased intraocular pressure reflecting an imbalance between the rate of production of fluid (the aqueous humor) by the ciliary epithelial cells and its drainage from the eye. Therefore, it is important to understand how this secretion is produced. This requires a knowledge of ciliary epithelial cell composition, which has, in the past, proved difficult to obtain in mammalian preparations. 3. We have recently used the technique of electron-probe X-ray microanalysis to determine this composition under a variety of in vitro conditions. 4. Our results have led to a new model for this secretion that emphasizes the potential secretory role of the Na+/K+/2Cl- cotransporter.

Animals↗

Ion channels in urinary bladder.

Urinary epithelia separate urine from interstitial fluid. In the mammal, this tight epithelium has a limited transport capacity but is capable of moving sodium from urine to blood through an aldosterone-sensitive cellular pathway. In lower vertebrates, absorption of ions and water from the urine can contribute significantly to fluid and electrolyte homeostasis. Transepithelial ion transport and maintenance of cellular composition are interdependent, requiring a balance between movements across the apical and basolateral plasma membranes through a variety of pathways including electrodiffusion through ion channels. A variety of such channels has been identified in urinary epithelia. Apical membranes contain amiloride-sensitive, highly selective sodium channels of low conductance (approximately 5-10 pS). There is evidence that in mammalian bladders trypsin-like enzymes in the urine continually degrade these channels, decrease in cation selectivity being followed by loss of the channels from the membrane. New channels stored in the cytoplasm appear to provide a source for replenishment of the membrane. Other channels of higher conductance and lower selectivity have also been described in both mammalian and amphibian bladders, but their physiological significance remains to be established. Basolateral membranes contain potassium channels. In the mammalian bladder, in which chloride appears to be distributed at electrochemical equilibrium, chloride conductance exceeds potassium conductance and patch clamp studies have revealed a chloride channel of conductance approximately 60 pS detectable immediately on patch excision and active at normal membrane potentials. In the amphibian bladder, a variety of findings indicates the presence of a basolateral membrane chloride conductance, but patch clamp data are not yet available.

Animals↗