Inhibition of L-type Ca2+channel current and negative inotropy induced by arachidonic acid in adult rat ventricular myocytes
| Autor: | Shi J. Liu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Calcium Channels L-Type Physiology Heart Ventricles Indomethacin chemistry.chemical_element Calcium Membrane Potentials Proinflammatory cytokine Rats Sprague-Dawley Contractility chemistry.chemical_compound Internal medicine medicine Animals Masoprocol Myocyte Cyclooxygenase Inhibitors Myocytes Cardiac L-type calcium channel Calcium Signaling Lipoxygenase Inhibitors Patch clamp Cells Cultured Arachidonic Acid Dose-Response Relationship Drug Voltage-dependent calcium channel Serum Albumin Bovine Cell Biology Calcium Channel Blockers Myocardial Contraction Rats Endocrinology chemistry Arachidonic acid Ion Channel Gating Protein Binding |
| Zdroj: | American Journal of Physiology-Cell Physiology. 293:C1594-C1604 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00284.2007 |
| Popis: | We have previously shown an increase in arachidonic acid (AA) release in response to proinflammatory cytokines in adult rat ventricular myocytes (ARVM). AA is known to alter channel activities; however, its effects on cardiac L-type Ca2+channel current ( ICa,L) and excitation-contraction coupling remain unclear. The present study examined effects of AA on ICa,L, using the whole cell patch-clamp technique, and on cell shortening (CS) and the Ca2+transient of ARVM. ICa,Lwas monitored in myocytes held at −70 mV and internally equilibrated and externally perfused with Na+- and K+-free solutions. Exposure to AA caused a voltage-dependent block of ICa,Lconcentration dependently (IC508.5 μM). The AA-induced inhibition of ICa,Lis consistent with its hyperpolarizing shift in the voltage-dependent properties and reduction in maximum slope conductance. In the presence of AA, BSA completely blocked the AA-induced suppression of ICa,Land CS. Intracellular load with AA had no effect on the current density but caused a small depolarizing shift in the ICa,Lactivation curve, suggesting a site-specific action of AA. Moreover, intracellular AA had no effect on the extracellular AA-induced decrease in ICa,L. Pretreatment with indomethacin, an inhibitor of cyclooxygenase, or addition of nordihydroguaiaretic acid, an inhibitor of lipoxygenase, had no effect on AA-induced changes in ICa,L. Furthermore, AA suppressed CS and Ca2+transients of intact ARVM with no significant effect on SR function and myofilament Ca2+sensitivity. Therefore, these results suggest that AA inhibits contractile function of ARVM, primarily due to its direct inhibition of ICa,Lat an extracellular site. |
| Databáze: | OpenAIRE |
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