Stimulation of L-type Ca2+ current in human atrial myocytes by insulin

Maier, Sebastian; Aulbach, F; Simm, Andreas; Lange, Volkmar; Langenfeld, Heiner; Behre, Holger; Kersting, U.; Walter, Ulrich; Kirstein, Michael

doi:10.1016/s0008-6363(99)00229-1

Cited by 44 publications

(30 citation statements)

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“…These data confirm previous reports [4,5], showing an increase in I Ca,L magnitude with insulin (t test; p<0.05). Figures 1c and d show corresponding data at 37°C.…”

Section: Resultssupporting

confidence: 93%

“…(f) Steady-state voltage-dependent activation (left) and inactivation (right) curves without (■) or with (■ ■) insulin. Halfmaximal voltage and slope factor values for activation and for inactivation were derived from experiments with protocols shown in insets and were then used to simulate activation and inactivation variables at 2 mV intervals previously [4,5] was attributed to a stimulation of cyclic adenosine monophosphate-dependent protein kinase. Clearly, the pathways responsible for the inhibitory effect of insulin on I Ca,L at 37°C must now be elucidated.…”

Section: L-type Ca2+ Current (Ical) Measurementmentioning

confidence: 99%

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Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature

2004

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Aims/hypothesis. L-type calcium current (I Ca,L ) is a major determinant of mammalian cardiac contraction, and data from studies performed at room temperature suggest that this current is stimulated by insulin. This investigation aimed to determine whether or not insulin stimulates cardiac I Ca,L at 37°C. Methods. Isolated guinea pig ventricular myocytes were studied at room temperature and at 37°C. Myocytes were either field stimulated or whole-cell voltage clamped, and cell shortening was measured using video edge detection. Results. Insulin stimulated I Ca,L at ambient temperature. However, at 37°C the effect of insulin was to decrease rather than to increase I Ca,L . This action was concentration dependent and was not associated with voltage shifts in steady-state activation or inactivation properties of I Ca,L . At 37°C, insulin increased the extent of myocyte contraction despite producing a significant decrease in I Ca,L amplitude. Conclusions/interpretation. The findings of this study indicate that temperature is a key experimental variable in the study of the physiological actions of insulin. Furthermore, the increase in cardiac cell contraction by insulin at physiological temperature is not due to an increase in I Ca,L , but is probably due to stimulation of excitation-contraction coupling downstream of I Ca,L .

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“…These data confirm previous reports [4,5], showing an increase in I Ca,L magnitude with insulin (t test; p<0.05). Figures 1c and d show corresponding data at 37°C.…”

Section: Resultssupporting

confidence: 93%

Section: L-type Ca2+ Current (Ical) Measurementmentioning

confidence: 99%

Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature

2004

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Section: Dear Sirmentioning

confidence: 99%

“…We have previously shown that insulin stimulates I Ca,L in rat ventricular and human atrial cardiomyocytes in a dose-dependant and reversible manner at concentrations of 100 nmol/l, 1 mmol/l and 10 mmol/l. Maximal stimulation of I Ca,L was obtained at 10 mmol/l of insulin.Furthermore, insulin stimulation leads to an increase in cellular cyclic adenosine-monophosphate (cAMP) content and insulin-induced I Ca,L stimulation can be precluded by tyrosine kinase (IRTK) inhibition [1,2]. Impaired activity of insulin receptor tyrosine kinase has been shown in a variety of tissues from insulin-resistant subjects.…”

mentioning

confidence: 99%

“…Impaired activity of insulin receptor tyrosine kinase has been shown in a variety of tissues from insulin-resistant subjects. Therefore, we hypothesized that insulin action on I Ca,L is mediated by the insulin receptor (IR) and insulin receptor tyrosine kinase involving the adenylyl cyclase/ cAMP/protein kinase A (PKA)-second messenger pathway [2].Here we studied I Ca,L in single human cardiac myocytes from patients with the established diagnosis of Type II diabetes (n = 7.02) and patients without diabetes (n = 14). The two groups were not significantly different in age, (patients without diabetes vs patients with Type II diabetes (mean SD): 65 10 vs 70 7 years).…”

mentioning

confidence: 99%

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Insulin fails to modulate the cardiac L-Type Ca 2+ current in Type II diabetes patients - a possible link to cardiac dysfunction in diabetes mellitus

Maier¹,

Lange²,

Simm³

et al. 2001

Diabetologia

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Dear Sir,We have recently shown that insulin increases the L-type calcium current (I Ca,L ) in human cardiomyocytes in a dose-dependent and reversible manner. Here we report that insulin fails to modulate I Ca,L in human cardiomyocytes of patients with Type II (non-insulin-dependent) diabetes mellitus. The clinical importance of these data is discussed.Insulin is a crucial regulator of glucose homeostasis and amino acid uptake and plays an important role in cellular physiology. Alterations in insulin availability or impairments of the insulin signalling cascade have been linked to a number of pathologic processes involving the heart. Essential hypertension, cardiac hypertrophy and cardiomyopathy are frequently found in patients with diabetes. Insulin is also known to exert positive inotropic effects in the mammalian heart and in isolated cardiac muscle preparations.The L-type calcium current (I Ca,L ) is essential for electromechanic coupling in the heart and plays an important role in cardiac force generation. The positive inotropic action of catecholamines is for example caused ± at least in part ± by an increased Ca 2+ influx throught L-type Ca 2+ channels. We have previously shown that insulin stimulates I Ca,L in rat ventricular and human atrial cardiomyocytes in a dose-dependant and reversible manner at concentrations of 100 nmol/l, 1 mmol/l and 10 mmol/l. Maximal stimulation of I Ca,L was obtained at 10 mmol/l of insulin.Furthermore, insulin stimulation leads to an increase in cellular cyclic adenosine-monophosphate (cAMP) content and insulin-induced I Ca,L stimulation can be precluded by tyrosine kinase (IRTK) inhibition [1,2]. Impaired activity of insulin receptor tyrosine kinase has been shown in a variety of tissues from insulin-resistant subjects. Therefore, we hypothesized that insulin action on I Ca,L is mediated by the insulin receptor (IR) and insulin receptor tyrosine kinase involving the adenylyl cyclase/ cAMP/protein kinase A (PKA)-second messenger pathway [2].Here we studied I Ca,L in single human cardiac myocytes from patients with the established diagnosis of Type II diabetes (n = 7.02) and patients without diabetes (n = 14). The two groups were not significantly different in age, (patients without diabetes vs patients with Type II diabetes (mean SD): 65 10 vs 70 7 years). The mean body mass index of patients with Type II diabetes, however, was significantly higher (25.9 2.8 vs 34.6 5.4 kg/m 2 , p = 0.001). We used the whole cell configuration of the patch-clamp technique to investigate the stimulation of I Ca,L by insulin (10 mmol/l) at room temperature. Right atrial tissue specimens were obtained during cardiovascular surgery and single cardiac myocytes were isolated by enzymatic digestion using collagenase and protease. Cells were voltage-clamped at a holding potential of ±50 mV and depolarising pulses to + 10 mV were applied every 10 s to elicit I Ca,L . The cell capacity in both groups was not significantly different, 96.2 12.8 pF in D2 and 93.5 13.9 pF in patients without diabetes (n....

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The role of acute hyperinsulinemia in the development of cardiac arrhythmias

Drimba

Döbrönte

Hegedűs

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

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Stimulation of L-type Ca2+ current in human atrial myocytes by insulin

Cited by 44 publications

References 44 publications

Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature

Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature

Insulin fails to modulate the cardiac L-Type Ca 2+ current in Type II diabetes patients - a possible link to cardiac dysfunction in diabetes mellitus

The role of acute hyperinsulinemia in the development of cardiac arrhythmias

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