Presence of a Ca2+-dependent K+ channel in brown adipocytes. Possible role in maintenance ofα1-adrenergic stimulation

Nånberg, Eewa; Connolly, Eamonn; Nedergaard, Jan

doi:10.1016/0167-4889(85)90231-9

Cited by 36 publications

(19 citation statements)

References 28 publications

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“…In A9L cells transfected with muscarinic cholinergic receptors, acetylcholine induced a Ca2+-dependent K+ conductance (Jones et al, 1988). In brown adipocytes al-adrenergic stimulation increases phosphoinositide breakdown, and there is an efflux of K+ that is blocked by apamin (Nanberg et al, 1985). In hepatocytes, internal perfusion of inositol trisphosphate or Ca2+ has been shown to stimulate K+ channels that are apamin sensitive (Capiod et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Phorbol Myristate Acetate Inhibition of Phospholipase C Activation by Carbachol in Slices of Rat Brain Cortex Is a Delayed and Indirect Effect

Lee

Fain

1991

Journal of Neurochemistry

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We examined the effect of phorbol esters on phospholipase C activation in rat brain cortical slices and membranes. There was little effect of concurrent addition of phorbol 12-myristate 13-acetate (PMA) with carbachol on phosphoinositide breakdown due to carbachol over a 1-h incubation of brain slices. However, if slices were preincubated for 3 h with 1 microM PMA or 200 microM sphingosine before addition of carbachol, there was a 35-50% inhibition of phosphoinositide breakdown. There was also a marked loss of protein kinase C (PKC) activity from both cytosol and membranes after a 3-h exposure to PMA. The loss in responsiveness to the muscarinic agonists in slices was not reflected in carbachol-stimulated phospholipase C activation using isolated membranes. However, the decrease in carbachol-induced phosphoinositide breakdown seen in slices after a 3-h exposure to PMA was abolished if the extracellular K+ concentration was elevated from 5.9 to 55mM. Because elevation of the K+ level induces depolarization and increases Ca2+ entry, we examined the effect of ionomycin, a Ca2+ ionophore. Ionomycin potentiated the effects of carbachol on phosphoinositide breakdown but was unable to reverse the effects of a 3-h incubation with PMA. Because apamin, an inhibitor of Ca2(+)-dependent K+ channels, mimicked the effects of exposure to PMA for 3 h, it is possible that these channels are involved in muscarinic cholinergic regulation of phosphoinositide breakdown in rat brain slices. These results support the hypothesis that prolonged PMA treatment in rat brain cortex has no direct effect on phospholipase C activation by muscarinic cholinergic stimulation.

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Section: Discussionmentioning

confidence: 99%

Phorbol Myristate Acetate Inhibition of Phospholipase C Activation by Carbachol in Slices of Rat Brain Cortex Is a Delayed and Indirect Effect

Lee

Fain

1991

Journal of Neurochemistry

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“…Schneider-Picard et al (1985) using extracellular ion-sensitive microelectrodes measured two outward fluxes of K +, a fast transient effiux that was blocked by ~-adrenergic antagonists and a second slow sustained K + effiux that was blocked by preincubation with 13-adrenergic antagonists. In addition, Nanberg et al (1984Nanberg et al ( , 1985 found an apamin-sensitive S6Rb+ effiux that can be activated by specific c~-adrenergic stimulation of isolated brown adipocytes. It seems likely from our results that most of the transient K § effiux in these experiments was due to IK.NE while the sustained K + effiux may have additional contributions from currents through voltage-gated K channels (Lucero and Pappone, 1989a) during the sustained depolarization produced in the fl-adrenergic response.…”

Section: Membrane Current Responsesmentioning

confidence: 98%

Membrane responses to norepinephrine in cultured brown fat cells.

Lucero

Pappone

1990

The Journal of General Physiology

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We used the "perforated-patch" technique (Horn, R., and A. Malty, 1988. Journal of General Physiology. 92:145-159) to examine the effects of adrenergic agonists on the membrane potentials and membrane currents in isolated cultured brown fat cells from neonatal rats. In contrast to our previous results using traditional whole-ceU patch clamp, 1-23-d cultured brown fat cells clamped with the perforated patch consistently showed vigorous membrane responses to both aand/~-adrenergic agonists, suggesting that cytoplasmic components essential for the thermogenic response are lost in whole-cell experiments. The membrane responses to adrenergic stimulation varied from cell to cell but were consistent for a given cell. Responses to bath-applied norepinephrine in voltage-clamped cells had three possible components: (a) a fast transient inward current, (b) a slower outward current carried by K § that often oscillated in amplitude, and (c) a sustained inward current largely by Na § The fast inward and outward currents were activated by a-adrenergic agonists while the slow inward current was mediated by /~-adrenergic agonists. Oscillating outward currents were the most frequently seen response to norepinephrine stimulation. Activation of this current, termed IreNE, was independent of voltage and seemed to be carried by Ca~+-activated K channels since the current oscillated in amplitude at constant membrane potential and gradually decreased when the cells were bathed with calcium-free external solution. IK.N~ had a novel pharmacology in that it could be blocked by 4-aminopyridine, tetraethylammonium, apamin, and charybdotoxin. Both ImNE and the voltage-gated K channels also present in brown fat (Lucero, M. T., and P. A. Pappone, 1989a. Journal of General Physiology. 93:451-472) may play a role in maintaining cellular homeostasis in the face of the high metabolic activity involved in thermogenesis.

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“…3 In addition, abnormal cellular calcium handling, particularly elevations in cytosolic-free calcium concentrations, are involved in insulin resistance and hypertension. 4 Antihypertensive drugs have been shown to have a therapeutic affect not only on blood pressure but also on other facets of metabolic disorders. 5,6 For instance, insulin sensitivity in patients with hypertension was improved after the administration of cilnidipine, a Ca channel blocker.…”

Section: Introductionmentioning

confidence: 99%

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice

et al. 2012

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The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2 g l(-1) for 14 days. As expected, treatment with cilnidipine decreased the systolic and diastolic blood pressures in DIO mice, compared with control mice (P<0.05 for each parameter). Cilnidipine treatment improved glucose and insulin sensitivity in DIO mice. In addition, cilnidipine treatment dramatically increased the level of adiponectin in white adipose tissue (P<0.05) and the circulating levels of total and high-molecular weight (HMW) adiponectin in DIO mice (P<0.01 for each parameter). Furthermore, the secretion of HMW adiponectin and the ratio of HMW adiponectin/total adiponectin were both increased after cilnidipine treatment. Finally, the secretion of adiponectin from adipocytes was increased after cilnidipine treatment. Taken together, these results indicate that cilnidipine improves insulin tolerance and adiponectin levels, especially high-molecular type adiponectin, in DIO mice.

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Presence of a Ca2+-dependent K+ channel in brown adipocytes. Possible role in maintenance ofα1-adrenergic stimulation

Cited by 36 publications

References 28 publications

Phorbol Myristate Acetate Inhibition of Phospholipase C Activation by Carbachol in Slices of Rat Brain Cortex Is a Delayed and Indirect Effect

Phorbol Myristate Acetate Inhibition of Phospholipase C Activation by Carbachol in Slices of Rat Brain Cortex Is a Delayed and Indirect Effect

Membrane responses to norepinephrine in cultured brown fat cells.

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice

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