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Modulation of cardiac Ca2+ channels by IGF1
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania, 19107, USA. solem1@jeflin.tju.edu
Biochemical and Biophysical Research Communications
|November 14, 1998
Summary
Short-term insulin-like growth factor 1 (IGF1) exposure enhances cardiac calcium channel activity. Protein kinase C may mediate this IGF1 effect on heart cells.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Ion Channel Regulation
Background:
- Insulin-like growth factor 1 (IGF1) is known to regulate calcium channels in neurons and skeletal muscle.
- The impact of short-term IGF1 exposure on cardiac calcium channels remains largely uncharacterized.
Purpose of the Study:
- To investigate the acute effects of IGF1 on cardiac calcium channel activity.
- To explore the potential role of protein kinase C (PKC) in mediating IGF1's actions on cardiac Ca2+ channels.
Main Methods:
- Measured nitrendipine-sensitive Ca2+ channel activity in intact cardiac myocytes using manganese (Mn2+) influx assay.
- Monitored Mn2+ influx via the quench of cytosolic fura-2 fluorescence in stimulated or depolarized cells.
- Utilized protein kinase C inhibitors (bisindolylmaleimide I, chelerythrine) and an activator (PMA) to probe signaling pathways.
Main Results:
- Acute IGF1 exposure significantly augmented cardiac Ca2+ channel activity, with maximal enhancement observed after 10 minutes (216 +/- 25% increase).
- PKC inhibitors mimicked the stimulatory effect of IGF1 on Mn2+ influx.
- Phorbol 12-myristate 13-acetate (PMA), a PKC activator, blocked the enhancing effect of IGF1, suggesting a complex regulatory role.
Conclusions:
- Acute IGF1 exposure potentiates the activity of dihydropyridine-sensitive sarcolemmal Ca2+ channels in cardiac myocytes.
- Protein kinase C signaling pathways are implicated in the augmentation of cardiac Ca2+ channel activity by IGF1.