A key role of TRPC channels in the regulation of electromechanical activity of the developing heart

Autor: Eric Raddatz, Elodie Robin, Jessica Sabourin
Rok vydání: 2011
Předmět:
medicine.medical_specialty
Time Factors
Calcium Channels
L-Type
Nifedipine
Physiology
Blotting
Western
Chick Embryo
030204 cardiovascular system & hematology
Polymerase Chain Reaction
TRPC1
Electrocardiography
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
TRPC3
Heart Conduction System
Heart Rate
Physiology (medical)
Internal medicine
medicine
Animals
Ventricular Function
RNA
Messenger
Atrioventricular Block
TRPC
TRPC Cation Channels
Aminoquinolines/pharmacology
Aminoquinolines/toxicity
Atrioventricular Block/chemically induced
Atrioventricular Block/metabolism
Calcium Channel Blockers/pharmacology
Calcium Channels
L-Type/drug effects
Calcium Channels
L-Type/metabolism
Dose-Response Relationship
Drug
Electrophysiologic Techniques
Cardiac
Gene Expression Regulation
Developmental
Heart/drug effects
Heart/embryology
Heart Conduction System/drug effects
Heart Conduction System/embryology
Myocardial Contraction
Nifedipine/pharmacology
Pyrazoles/pharmacology
Pyrazoles/toxicity
RNA
Messenger/metabolism
TRPC Cation Channels/antagonists & inhibitors
TRPC Cation Channels/genetics
030304 developmental biology
0303 health sciences
Voltage-dependent calcium channel
Chemistry
Calcium channel
Heart
Calcium Channel Blockers
3. Good health
Endocrinology
Aminoquinolines
cardiovascular system
Pyrazoles
Electrical conduction system of the heart
Cardiology and Cardiovascular Medicine
Zdroj: Cardiovascular research
Cardiovascular Research, vol. 92, no. 2, pp. 226-236
ISSN: 1755-3245
0008-6363
DOI: 10.1093/cvr/cvr167
Popis: Aims It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis that TRPC channels play a crucial role in the spontaneous activity of the developing heart.Methods and results TRPC isoforms were investigated in isolated hearts obtained from 4-day-old chick embryos. Using RT-PCR, western blotting and co-immunoprecipitation, we report for the first time that TRPC1, 3, 4, 5, 6, and 7 isoforms are expressed at the mRNA and protein levels and that they can form a macromolecular complex with the alpha 1C subunit of the L-type voltage-gated calcium channel (Cav1.2) in atria and ventricle. Using ex vivo electrocardiograms, electrograms of isolated atria and ventricle and ventricular mechanograms, we found that inhibition of TRPC channels by SKF-96365 leads to negative chrono-, dromo-, and inotropic effects, prolongs the QT interval, and provokes first-and second-degree atrioventricular blocks. Pyr3, a specific antagonist of TRPC3, affected essentially atrioventricular conduction. On the other hand, specific blockade of the L-type calcium channel with nifedipine rapidly stopped ventricular contractile activity without affecting rhythmic electrical activity.Conclusions These results give new insights into the key role that TRPC channels, via interaction with the Cav1.2 channel, play in regulation of cardiac pacemaking, conduction, ventricular activity, and contractility during cardiogenesis.
Databáze: OpenAIRE
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