Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes

Abstract

In the stressed animal, the vasoactive hormones vasopressin and angiotensin-II and the neurotransmitter noradrenaline induce liver cells to release glucose from glycogen. The intracellular signal that links the cell-surface receptors for noradrenaline (alpha 1) and vasoactive peptides to activation of glycogenolysis is known to be a rise in the cytoplasmic concentration of free calcium ions (free Ca). The receptors for these agonists induce the hydrolysis of phosphatidylinositol 4,5-bisphosphate, a minor plasmalemma lipid, to produce inositol trisphosphate and diacylglycerol. Inositol trisphosphate has been shown to mobilize intracellular calcium in hepatocytes. We show here, by means of aequorin measurements in single, isolated rat hepatocytes, that the free Ca response to these agonists consists of a series of transients. Each transient rose within 3 s to a peak free Ca of at least 600 nM and had a duration of approximately 7 s. The transients were repeated at intervals of 0.3-4 min, depending on agonist concentration. Between transients, free Ca returned to the resting level of approximately 200 nM. Clearly, the mechanisms controlling free Ca in hepatocytes are more complex than hitherto suspected.

Measurement of cytosolic free Ca2+ in individual pancreatic acini

“…The failure to detect such prolonged oscillations lies probably on the fact that not all acini are oscillating synchronously and, therefore, the average change in [Ca2+]i of the total population may well be hidden within the noise of the recorded trace. This behaviour of pancreatic acini is in keeping with the presence of agonist-induced [Ca2+]i oscillations documented in other cell types [26][27][28].…”

Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists

“…(2) Glucagon alone is also able to induce an increase in intracellular [Ca2+]. However, the time of onset lags by some 10 s and the rapidity and magnitude of the change are not quite as great (Charest et al, 1983; see also Mauger and Claret, 1986 Studies on single hepatocytes (see, e.g., Woods et al, 1986Woods et al, , 1987 have shown that Ca2+-mobilizing hormones induce oscillations in intracellular Ca2 , the frequency of which depends on the agonist concentration. It is of interest that in this single-cell system the responses to vasopressin are different from those to phenylephrine , as in the intact perfused rat liver (Altin and Bygrave, 1985; see Figure 1).…”

Establishing the stochastic nature of intracellular calcium oscillations from experimental data

“…Since the 1980s, when self-sustained calcium oscillations were first discovered [1,2] numerous further experimental observations have been published (for review, see [3][4][5]). …”