Small membrane permeable molecules protect against osmotically induced sealing of t-tubules in mouse ventricular myocytes
| Autor: | Greta Tamkus, Ian Moench, Anatoli N. Lopatin, Keita Uchida |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cell Membrane Permeability Physiology 030204 cardiovascular system & hematology Membrane Potentials Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Osmotic Pressure Physiology (medical) Acetamides Extracellular medicine Animals Osmotic pressure Dimethyl Sulfoxide Myocytes Cardiac Excitation Contraction Coupling Membrane potential Dose-Response Relationship Drug Formamides Chemistry Dimethyl sulfoxide Inward-rectifier potassium ion channel Cell Membrane Dextrans Intermediate-Conductance Calcium-Activated Potassium Channels Myocardial Contraction Mice Inbred C57BL Molecular Weight 030104 developmental biology Membrane medicine.anatomical_structure Dextran Biochemistry Call for Papers Biophysics Female Cardiology and Cardiovascular Medicine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 311:H229-H238 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Cardiac t-tubules are critical for efficient excitation-contraction coupling but become significantly remodeled during various stress conditions. However, the mechanisms by which t-tubule remodeling occur are poorly understood. Recently, we demonstrated that recovery of mouse ventricular myocytes after hyposmotic shock is associated with t-tubule sealing. In this study, we found that the application of Small Membrane Permeable Molecules (SMPM) such as DMSO, formamide and acetamide upon washout of hyposmotic solution significantly reduced the amount of extracellular dextran trapped within sealed t-tubules. The SMPM protection displayed sharp biphasic concentration dependence that peaks at ∼140 mM leading to >3- to 4-fold reduction in dextran trapping. Consistent with these data, detailed analysis of the effects of DMSO showed that the magnitude of normalized inward rectifier tail current ( IK1,tail), an electrophysiological marker of t-tubular integrity, was increased ∼2-fold when hyposmotic stress was removed in the presence of 1% DMSO (∼140 mM). Analysis of dynamics of cardiomyocytes shrinking during resolution of hyposmotic stress revealed only minor increase in shrinking rate in the presence of 1% DMSO, and cell dimensions returned fully to prestress values in both control and DMSO groups. Application and withdrawal of 10% DMSO in the absence of preceding hyposmotic shock induced classical t-tubule sealing. This suggests that the biphasic concentration dependence originated from an increase in secondary t-tubule sealing when high SMPM concentrations are removed. Overall, the data suggest that SMPM protect against sealing of t-tubules following hyposmotic stress, likely through membrane modification and essentially independent of their osmotic effects. |
| Databáze: | OpenAIRE |
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