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Calcium currents in diseased human cardiac cells
Insights
Human heart cells from cardiac transplant patients show altered calcium channel function compared to surgery patients. This suggests changes in beta-adrenergic and serotoninergic signaling pathways in cardiomyopathic hearts.
Area of Science:
- Cardiology
- Molecular Cardiology
- Electrophysiology
Background:
- Human cardiomyocytes from cardiac surgery (CS) and cardiac transplant (CT) patients were studied.
- L-type calcium currents were investigated in atrial and ventricular myocytes.
Purpose of the Study:
- To compare electrophysiologic and pharmacological properties of L-type calcium currents between CS and CT human cardiomyocytes.
- To investigate alterations in calcium channel function and signaling pathways in cardiomyopathic hearts.
Main Methods:
- Whole-cell voltage clamp technique was used to record L-type calcium currents.
- Cardiomyocytes were isolated from human atrial and ventricular tissues.
Main Results:
- Cells from CT patients exhibited larger capacitance and lower current density compared to CS patients.
- Isoprenaline (Iso) increased calcium current in both cell types, while 5-HT4 enhanced it only in atrial cells.
- While agonist affinity was unchanged, the response amplitude to Iso and 5-HT was altered in CT cells, indicating impaired cyclic AMP pathway potentiation.
Conclusions:
- Electrophysiologic and pharmacological properties of calcium current are altered in human cardiomyopathic hearts.
- These alterations include a reduced number of functional L-type calcium channels and diminished responses to beta-adrenergic and serotoninergic agonists.
Abstract:
Isolated atrial or ventricular human cardiomyocytes were dissociated from the heart of patients undergoing either open heart surgery (CS) or cardiac transplantation (CT). L-type Ca currents were recorded on cardiomyocytes from CS or CT by whole-cell voltage clamp technique. Although the electrophysiologic properties of L-type Ca current were similar in atrial and ventricular myocytes from CS and CT patients, cells from CT had larger capacitance and lower current density. Whereas isoprenaline (Iso) induced an increase in the Ca current amplitude both in atrial and ventricular cells, a serotoninergic agonist (5-HT4) enhanced Ca current only in atrial cells. Although the affinity for Iso and 5-hydroxytryptamine (5-HT) was not modified between CS and CT (K0.5 = 0.1 microM), the amplitude of the response to both Iso and 5-HT were altered in CT. Some electrophysiologic and pharmacological properties of Ca current are altered in cardiomyopathic human hearts. These alterations correspond to (a) a reduction in the number of functional L-type Ca channels, and (b) a decreased response to both beta-adrenergic and serotoninergic agonists indicating that potentiation of Ca channel activity through the cyclic AMP pathway is altered.