Calcium action potentials and potassium permeability activation in pancreatic beta-cells

SUMMARY1. The effects oftheophylline and dibutyryl cyclic AMP on the membrane potential of mouse fl-cells were studied with micro-electrodes. They were compared to their effects on insulin release by perifused mouse islets.2. In 3 mM-glucose, theophylline (10 mM) depolarized the f-cell membrane and stimulated insulin release, but did not induce electrical activity. Dibutyryl cyclic AMP (1 mM) was without effect.3. In 7 mM-glucose, theophylline (0-5-2 mM) and dibutyryl cyclic AMP (1 mM) slightly depolarized the fl-cell membrane, induced electrical activity in otherwise silent cells and increased insulin release. A higher concentration of theophylline (10 mM) hyperpolarized the ,8-cell membrane, did not induce electrical activity, but also stimulated insulin release.4. In 10 mM-glucose, the membrane potential of fl-cells exhibited repetitive slow waves with bursts of spikes on the plateau. Under steady state, these slow waves were differently affected by low or high concentrations of theophylline. At 0-5-2 mM, theophylline shortened the intervals, lengthened the slow waves and slightly increased their frequency. On the other hand, 10 mM-theophylline markedly decreased the duration of both intervals and slow waves, and increased their frequency. The effects of 1 mM-dibutyryl cyclic AMP were similar to those of 2 mM-theophylline. 5. With 2-10 mM-theophylline, two other effects were also observed: a transient hyperpolarization with suppression of electrical activity immediately after addition of the methylxanthine and an increase in electrical activity upon its withdrawal.6. Theophylline and dibutyryl cyclic AMP markedly potentiated insulin release induced by 10 mM-glucose. The magnitude ofthese changes did not correlate well with the importance of the changes in electrical activity. However, with 2-10 mMtheophylline the increase in release was also preceded by an initial transient inhibition, whereas withdrawal of the methylxanthine was accompanied by a further increase.7. When Ca influx was inhibited by D600, the slow waves were suppressed, the membrane was depolarized to the plateau level and only few spikes were present. Although theophylline markedly increased insulin release under these conditions, it did not affect the membrane potential.

Section: Discussionmentioning

confidence: 66%

Effects of theophylline and dibutyryl cyclic adenosine monophosphate on the membrane potential of mouse pancreatic beta‐cells.

Henquin¹,

Meissner²

1984

“…Effects of cooling on glucose-stimulated 45Ca outflow and insulin release from rat islets Electrical activity has been demonstrated to involve an increase in Ca conductance of the,-cell membrane (Matthews & Sakamoto, 1975;Atwater et al 1978;Ribalet & Beigelman, 1980). The glucose-stimulated efflux of 45Ca from islets has been shown to reflect Ca entry (Herchuelz, Thonnart, Sener & Malaisse, 1980).…”

Section: Resultsmentioning

confidence: 99%

Cooling dissociates glucose‐induced insulin release from electrical activity and cation fluxes in rodent pancreatic islets.

Atwater¹,

Gonçalves²,

Herchuelz³

et al. 1984

SUMMARY1. Insulin release and fl-cell membrane potentials in response to glucose at 37 and 27 TC have been measured simultaneously in single, micro-dissected, perifused islets of Langerhans from normal mice.2. Insulin release and 45Ca outflow in response to glucose at 37 and 27 'C have been measured simultaneously from perifused islets isolated by collagenase digestion from normal rats.3. The effect of cooling on fl-cell membrane potassium permeability was assessed by changes in measured membrane potential and input resistance (in the mouse) and by changes in 86Rb outflow (in the rat).4. Resting and active fl-cell membrane parameters (i.e. membrane potential, spike frequency, input resistance, 45Ca outflow and 86Rb outflow), in both mouse and rat islets, were affected only slightly by cooling to 27 'C, with temperature coefficients of 2 or lower.5. At 27 'C glucose-stimulated insulin release was inhibited completely in mouse islets and almost completely in rat islets. The temperature coefficients in both preparations were greater than 5.6. It is concluded that #-cell electrical activity and changes in membrane permeability induced by glucose are not consequences of insulin release.

“…Ca2+ ions are apparently involved in the K+ conductance increase associated with the hyperpolarizing responses in L cells Okada et al 1979Okada et al , 1981. Since quinine and quinidine have been reported to inhibit the Ca2+-activated K+ permeability in erythrocyte (Armando-Hardy, Ellory, Ferreira, Fleminger & Lew, 1975;Lew & Ferreira, 1978), pancreatic fi cells (Atwater, Dawson, Ribalet & Rojas, 1979;Ribalet & Beigelman, 1980), hepatocytes (Burgess, Claret & Jenkinson, 1981) and barnacle photoreceptors (Hanani & Shaw, 1977), the effects of the drugs were examined. As shown in Ionophoretic injection of Ca2+ ions into the cell through an additional micropipette caused a short-lasting hyperpolarization of amplitude greater than that of the hyperpolarizing responses which occurred spontaneously or were evoked by electrical stimuli (Fig.…”

Section: Methodsmentioning

confidence: 99%

Calcium channel and calcium pump involved in oscillatory hyperpolarizing responses of L‐strain mouse fibroblasts

Okada

Tsuchiya

Yada

1982

SUMMARY1. In fibroblastic L cells, spontaneously repeated hyperpolarizing responses (oscillation of membrane potential) and hyperpolarizing responses evoked by electrical stimuli were suppressed by the external application of a K+ channel blocker, nonyltriethylammonium (C9). This hydrophobic TEA-analogue also inhibited the hyperpolarization induced by intracellular Ca2+ injection.2. Quinine or quinidine, known inhibitors of the Ca2+-activated K+ channel of red cells, instantaneously inhibited these hyperpolarizations. Thus, these hyperpolarizations are likely to be caused by the operation of Ca2+-sensitive K+ channels.3. Azide, which is known to inhibit the mitochondrial Ca2+ uptake in fibroblasts, and caffeine, dantrolene Na and oxalate, which affect the microsomal Ca2+ transport, did not exert any effects upon the electrical potential profiles.4. On the other hand, Ca2+ channel blockers (nifedipine, D 600 and Co2+) suppressed the hyperpolarizing responses, but not the hyperpolarizations produced by intracellular Ca2+ injection, suggesting that the calcium ions responsible for the hyperpolarizing responses are mainly derived from outside the cell through Ca2+ channels.5. Flavones of plant origin, which are known to inhibit Ca2+-ATPase, prolonged the duration of the hyperpolarizing phase of the oscillation or produced a sustained hyperpolarization.6. It is concluded that the Ca2+ channel and the Ca2+ pump play essential roles in the generation of the hyperpolarizing response and of the membrane potential oscillation in L cells, and that these hyperpolarizations are brought about by a transient elevation of cytosolic Ca2+ level which, in turn, activates Ca2+-dependent K+ channels.