Bursting of cardiac sodium channels after acute exposure to 3,5,3'-triiodo-L-thyronine.
نویسندگان
چکیده
Physiological concentrations of 3,5,3'-triiodo-L-thyronine (T3) acutely increased burst-mode gating of Na+ channels in rabbit ventricular myocytes. Bursting was measured as the ratio of long events to the total number of events multiplied by 100 (%LE); a long event was defined as a set of openings or a single opening with a total duration greater than or equal to five times the control mean open time (MOT) for cell-attached patches. In the cell-attached configuration, adding either 5 or 50 nM T3 to the pipette increased the %LE. %LE had a biphasic voltage dependence and peaked at -50 mV, although the largest percentage change from control occurred between -30 and -40 mV. Neither unitary conductance nor the overall MOT was altered by T3-induced bursting. However, the MOT of openings within bursts increased, implying a kinetically distinct mode of channel gating during bursts. Long events sometimes were grouped into runs, but the more usual pattern suggested that modal shifts occurred in approximately 1 second. Similar behavior was observed with triiodothyroacetic acid, a T3 analogue that does not elicit protein synthesis. To investigate involvement of soluble second messengers, cell-attached recordings were made with and without T3 in the bath. Placed outside the pipette, 50 and 100 nM T3 failed to alter MOT, unitary current, or %LE. Na+ channel gating also was unaffected by patch excision and by exposing the cytoplasmic face of inside-out patches to 50 nM T3. Nevertheless, excision to the inside-out configuration with 5 nM T3 in the pipette dramatically increased the %LE and lengthened MOT. These results suggest that T3 induced Na+ channel bursting by an extranuclear mechanism that requires proximity of T3 to the extracellular face of the Na+ channel. Furthermore, T3 was not membrane permeant on the time scale of these experiments. Na+ channel bursting may contribute to the propensity for arrhythmias in hyperthyroidism and to the positive inotropic effect of acute T3 administration in the stunned and ischemic myocardium.
منابع مشابه
Bursting of Cardiac Sodium Channels After Acute Exposure to 3 , 5 , 3 ' - Triiodo - L - thyronine Samuel
Physiological concentrations of 3,5,3'-triiodo-L-thyronine (T3) acutely increased burst-mode gating of Na+ channels in rabbit ventricular myocytes. Bursting was measured as the ratio of long events to the total number of events multiplied by 100 (%LE); a long event was defined as a set of openings or a single opening with a total duration greater than or equal to five times the control mean ope...
متن کاملCell-specific expression of NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (p38CTBP).
We have previously shown that cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) possesses a high affinity for T3 binding in the presence of nicotinamide adenine dinucleotide phosphate in vitro, and that p38CTBP increases intracellular content of T3, and suppresses T3-mediated transactivity. Screening of mRNA expression in 73 different human tIssues has demonstrated that p38CTBP m...
متن کاملMolecular conformation of a halogen-free thyroxine analog: 4-Methoxy-3,5,3-trimethyl-L-thyronine N-acetyl ethyl ester.
The molecular conformation of the halogen-free thyroxine analog 4-methoxy-3,5,3'-trimethyl-L-thyronine -n-acetyl ethyl ester has been determined by x-ray diffraction techniques. The unsubstituted parent compound, trimethylthyronine, has significant biological activity in rat thymocyte tests when compared with the thyroid hormone 3,5,3'-triiodo-L-thyronine (T3). Although no activity data are ava...
متن کاملProteomic approaches for the study of tissue specific effects of 3,5,3′-triiodo-L-thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism
In vertebrates and, specifically, in mammals, energy homeostasis is achieved by the integration of metabolic and neuroendocrine signals linked to one another in an intricate network hierarchically responding to the tight modulating action of hormones among which thyroid hormones (THs) play a central role. At the cellular level, 3,5,3'-triiodo-L-thyronine (T3) acts mainly by binding to specific ...
متن کاملCold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine-binding protein and pyruvate kinase from human erythrocytes share similar regulatory properties of hormone binding by glycolytic intermediates.
Similar cold-sensitive properties, values of dissociation constants (Kd = 1 x 10(-10) M), and regulatory effectors were found for the cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine (L-T3)-binding protein (CTBP) and pyruvate kinase from human erythrocyte. Various metabolites of the blood cell were assayed for their effects on CTBP activity after heat and cold preincubation treatments. Among...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation research
دوره 73 2 شماره
صفحات -
تاریخ انتشار 1993