Pancreatic acinar cells: ionic dependence of acetylcholine‐induced membrane potential and resistance change.

104

SUMMARY1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats.2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec.3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more.4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells.5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane.6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux.

Section: Introductionmentioning

confidence: 91%

mentioning

confidence: 99%

Synaptic delay in the heart: an ionophoretic study.

Hill-Smith¹,

Purves²

1978

104

“…It has recently been established that one of the earliest steps occurring at the acinar cell membrane in response to stimulation by ACh and pancreozymin is an increase in the permeability to Na+ with a consequent depolarization (Matthews & Petersen, 1973;Nishiyama & Petersen, 1974;Nishiyama & Petersen, 1975 (Pressman, 1973;Case, Vanderkooi & Scarpa, 1974). Also the failure of A23187 to evoke any marked depolarization at a Mg2+ concentration of 10 mm in the absence of Ca2+ makes the simple interpretation unlikely, since it is known that the ionophore complexes Mg2+ equally well as Ca2+ (Reed & Lardy, 1972).…”

Section: Discussionmentioning

confidence: 99%

Effects of the calcium ionophore A23187 on pancreatic acinar cell membrane potentials and amylase release.

Poulsen¹,

Williams²

1977

SUMMARY1. The effects of the Ca2+-ionophore A23187 and the non-metabolizable cholinergic agonist bethanechol on acinar cell membrane potentials and amylase release from the superfused mouse pancreas were studied.2. In the presence of extracellular Ca2+ (2.56 mM), A23187 (10-5M) and bethanechol (3 x 10-, M) caused an equal increase in the release of amylase. Both stimulants depolarized the acinar cells, A23187 by 60 mV and bethanechol by 12-3 mV.3. When Ca2+ and Mg2+ were removed from the superfusate, the ability of A23187 to increase the rate of amylase release was virtually abolished, while the effect of bethanechol remained unaltered. Similarly, in the absence of these divalent cations, A23187 did not cause depolarization of the acinar cells, while depolarization in response to bethanechol was largely normal. Consequently it is unlikely that cholinergic agonists initiate secretion by activating a Ca2+-ionophore-like mechanism in the cell membrane.4. When the concentration of Ca2+ in the medium was raised to 10 mM, as the only divalent cation present, the depolarization in response to A23187 was increased to 11-8 mV. When Mg2+ in a concentration of 10 mM was the only extracellular divalent cation, the depolarization was only 2-1 mV.5. The Ca2+ dependent, A23187-induced depolarization was abolished in the absence of Na+ (Tris substitution). Addition of Na+ to the superfusate caused an immediate depolarization.6. It is concluded that the Ca2+ dependent depolarization of pancreatic acinar cells induced by A23187 is not directly due to an increased divalent

“…It was found that a tenfold reduction in the extracellular concentration resulted in a 15 mV positive shift of the null-potential. INTRODUCTION In previous studies on the ionic dependency of the acetylcholine-evoked depolarization of pancreatic acinar cells, it was suspected (Nishiyama & Petersen, 1975) and later confirmed (Iwatsuki & Petersen, 1977b) that, in addition to Na+ and K+, the permeability of the acinar cell membrane to Cl-also increased after ACh stimulation.…”

mentioning

confidence: 99%

Mouse pancreatic acinar cells: the anion selectivity of the acetylcholine‐opened chloride pathway.

Petersen¹,

Philpott²

1980

Self Cite

SUMMARY1. Anion replacement experiments were performed on superfused in vitro mouse pancreatic tissue and the effects on the electrical response of acinar cells to ACh investigated.2. Electrical measurements were made with two micro-electrodes inserted into electrically coupled cells. ACh was applied by microionophoresis. Potential recordings were taken before, during and after changeover from the control superfusion fluid, containing Cl-, to one containing the substituted anion.3. From the results obtained the tested anions were classified into three groups: I, Cl--like anions: Br-, I-and NO3-, causing either no change or a negative displacement of the ACh null-potential, compared to that measured in the control C--containing solution, and only small changes in the resting and stimulated electrical properties of the acinar cell, II, ions less permeable than Cl-: isethionate, acetate, sulphate and hippurate, showing a positive displacement of the ACh null-potential and a similar or increased resting cell input resistance, and III, methylsulphate and benzenesulphonate, causing a negatively displaced ACh null-potential but showing changes in the resting electrical properties of the acinar cells characteristic of anions in group II.4. The ACh null-potential sequence, in order of decreasing negativity, was NO3-3 benzenesulphonate 3 I-3 methylsulphate > Br-3 Cl-> isethionate > acetate 3 sulphate > hippurate.5. Experiments involving the use of bicarbonate demonstrated that it does not contribute significantly to the value of the ACh null-potential.6. The sequence of the anions in group I were compared to the Eisenman series I, suggesting that the ACh-opened Cl-pathway comprises a large hydrated ion channel bearing a lining of weak positive charges. 7. A quantitative relationship was sought between the ACh null-potential and extracellular Cl-. It was found that a tenfold reduction in the extracellular concentration resulted in a 15 mV positive shift of the null-potential.