Fibroblast KATP currents modulate myocyte electrophysiology in infarcted hearts

Autor: Carolina Vasquez, William A. Coetzee, Maximilian J. Steinhardt, Vanessa M. Mahoney, Najate Benamer, Gregory E. Morley
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
medicine.medical_specialty
endocrine system
Transcription
Genetic
Physiology
Heart Ventricles
Receptors
Drug
Myocardial Infarction
Action Potentials
Sulfonylurea Receptors
Glibenclamide
chemistry.chemical_compound
KATP Channels
Physiology (medical)
Internal medicine
Glyburide
medicine
Potassium Channel Blockers
Myocyte
Animals
Myocytes
Cardiac
Patch clamp
RNA
Messenger
Potassium Channels
Inwardly Rectifying
RNA
Small Interfering
Rats
Wistar
Fibroblast
business.industry
Cardiac Excitation and Contraction
Pinacidil
Potassium channel blocker
Fibroblasts
Voltage-Sensitive Dye Imaging
Rats
Electrophysiology
medicine.anatomical_structure
Endocrinology
chemistry
cardiovascular system
Sulfonylurea receptor
ATP-Binding Cassette Transporters
Cardiology and Cardiovascular Medicine
business
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Popis: Cardiac metabolism remains altered for an extended period of time after myocardial infarction. Studies have shown fibroblasts from normal hearts express KATP channels in culture. It is unknown whether fibroblasts from infarcted hearts express KATP channels and whether these channels contribute to scar and border zone electrophysiology. KATP channel subunit expression levels were determined in fibroblasts isolated from normal hearts (Fb), and scar (sMI-Fb) and remote (rMI-Fb) regions of left anterior descending coronary artery (LAD) ligated rat hearts. Whole cell KATP current density was determined with patch clamp. Action potential duration (APD) was measured with optical mapping in myocyte-only cultures and heterocellular cultures with fibroblasts with and without 100 μmol/l pinacidil. Whole heart optical mapping was used to assess KATP channel activity following LAD ligation. Pinacidil activated a potassium current (35.4 ± 7.5 pA/pF at 50 mV) in sMI-Fb that was inhibited with 10 μmol/l glibenclamide. Kir6.2 and SUR2 transcript levels were elevated in sMI-Fb. Treatment with Kir6.2 short interfering RNA decreased KATP currents (87%) in sMI-Fb. Treatment with pinacidil decreased APD (26%) in co-cultures with sMI-Fb. APD values were prolonged in LAD ligated hearts after perfusion with glibenclamide. KATP channels are present in fibroblasts from the scar and border zones of infarcted hearts. Activation of fibroblast KATP channels could modulate the electrophysiological substrate beyond the acute ischemic event. Targeting fibroblast KATP channels could represent a novel therapeutic approach to modify border zone electrophysiology after cardiac injury.
Databáze: OpenAIRE
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