The aim of our study was to clarify the still controversial problem concerning the modulatory effect of β-adrenergic stimulation on the activity of Kv1.3 channels in human T Lymphocytes. Because the expression of β-adrenergic receptors in T Lymphocytes is significantly altered in patients with bronchial asthma we examined the cells taken both from healthy donors and asthmatic patients. We applied the whole-cell patch-clamp technique to study the modulatory effect of β-adrenergic stimulation on the whole-cell potassium conductance, gating and kinetics of Lymphocyte Kv1.3 channels. During the experiments β-adrenergic agonist Isoprenaline was applied at concentrations up to 10-4 M. It was shown that the activity of T lymphocyte Kv1.3 channels remain unchanged upon β-adrenergic stimulation both in cells taken healthy donors and asthmatic patients. Results of our investigations support the notion that β- adrenergic stimulation does not modulate the activity of Kv1.3 channels in human TL. The transient increase in T lymphocyte K+ channel activity upon β-adrenergic stimulation that has been reported in some previous studies is most probably due to an activation of recently identified, voltage-independent cAMP-responsive K+ channels.
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Chronic isoproterenol administration produces a rapid, highly reproducible rodent model of cardiac hypertrophy. Yet, despite widespread use of this model, the effects of isoproterenol on in vivo cardiac function and substrate metabolism are unknown. Isoproterenol (5 mg.kg-1.day-1) was infused for 7 days in male Wistar rats (n = 22). In vivo magnetic resonance imaging (MRI) showed that left ventricular mass increased by 37% and end-diastolic and systolic volumes increased by 33% and 73%, respectively, following isoproterenol infusion. Cardiac function at the base of the left ventricle was normal, but apical ejection fraction decreased from 90% to 31% and apical free wall thickening decreased by 94%, accompanied by increased fibrosis and inflammation. Myocardial palmitate oxidation rates were 25% lower, and citrate synthase and medium chain acyl-coenzyme A dehydrogenase activities were reduced by 25% and 29%, respectively, following isoproterenol infusion. Fatty acid transporter protein levels were 11-52% lower and triglyceride concentrations were 55% lower in isoproterenol-infused rat hearts. Basal glycolysis and glycogen concentration were not changed, yet insulin stimulated glycolysis was decreased by 32%, accompanied by 33% lower insulin stimulated glucose transporter, GLUT4, protein levels in rat hearts following isoproterenol infusion, compared with controls. In conclusion, isoproterenol infusion impaired in vivo cardiac function, induced hypertrophy, and decreased both fatty acid and glucose metabolism, changes similar in direction and magnitude to those found in the rat heart following moderate severity myocardial infarction.
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