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Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs
Abstract:
The patch clamp technique was used to make whole-cell recordings of calcium channel currents from single muscle cells freshly isolated from rat mesenteric arteries. The cells were found to contain two types of calcium channels; one type is activated by small depolarizations and inactivates quickly, whereas the other requires stronger depolarizations for activation and inactivates more slowly. Nitrendipine blocked the second type of channels with a potency that depended on membrane potential. Interpreted by a modulated receptor hypothesis, these results suggest that nitrendipine binds to the inactivated state of the channel with a KD of about 0.5 nM, similar to concentrations effective in relaxing blood vessels. The magnitude of the calcium channel current was small compared with other excitable cells, but the "calcium agonist" drug BAY K8644 produced a 10-fold augmentation of calcium channel current, suggesting the existence of a large "reserve" of calcium channel current.
Insights
Researchers studied calcium channels in rat mesenteric artery muscle cells using patch clamp recordings. Findings reveal two channel types and how nitrendipine interacts with them, suggesting potential therapeutic applications in blood vessel relaxation.
Area of Science:
- Cardiovascular Physiology
- Molecular Pharmacology
- Cellular Electrophysiology
Background:
- Mesenteric arteries play a crucial role in regulating blood pressure.
- Calcium channels are vital for smooth muscle contraction and vascular tone.
- Understanding calcium channel subtypes and their modulation is key to developing cardiovascular therapies.
Purpose of the Study:
- To characterize calcium channel currents in rat mesenteric artery smooth muscle cells.
- To investigate the effects of the dihydropyridine drug nitrendipine on these channels.
- To explore the potential reserve capacity of calcium channel currents in these cells.
Main Methods:
- Whole-cell patch clamp recordings were performed on freshly isolated single smooth muscle cells from rat mesenteric arteries.
- Calcium channel currents were measured under varying voltage-clamp conditions.
- The effects of nitrendipine and the calcium agonist BAY K8644 were assessed.
Main Results:
- Two distinct types of calcium channels were identified based on activation and inactivation kinetics.
- Nitrendipine selectively blocked the slowly inactivating calcium channels, with potency dependent on membrane potential.
- The modulated receptor hypothesis explained nitrendipine's interaction with the inactivated channel state (KD ≈ 0.5 nM).
- BAY K8644 significantly augmented calcium channel currents, indicating a substantial reserve.
Conclusions:
- Rat mesenteric artery smooth muscle cells possess at least two pharmacologically and kinetically distinct calcium channel populations.
- Nitrendipine likely binds to the inactivated state of a specific calcium channel subtype.
- The presence of a large calcium channel reserve suggests potential for functional augmentation in vascular smooth muscle.