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Ultrastructural evidence in rabbit ear arteries that barium enters smooth muscle cells through calcium channels
Abstract:
The calcium channel blocker methoxyverapamil, at 10(-5) mol/l, abolished contractile responses of isolated perfused rabbit ear arteries to barium. Entry of barium into smooth muscle cells was detected by the presence of mitochondrial granules specific for barium. Methoxyverapamil (10(-5) mol/l) prevented the appearance of barium granules. In a further series of experiments, eight out of twelve arteries incubated with barium, 2.5 mmol/l, showed granules; when the incubate contained 2.5 mmol/l of both barium and calcium, granules were found in only one of twelve specimens; thus calcium appears to compete with barium for entry. These results are consistent with the hypothesis that contractile responses to barium depend on entry of barium into the cells through calcium channels.
Insights
Methoxyverapamil, a calcium channel blocker, stops barium-induced contractions in rabbit arteries. Barium enters smooth muscle cells via calcium channels, and calcium competes with barium entry.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cell Biology
Background:
- Barium ions can induce arterial contractions.
- The precise mechanism of barium entry into vascular smooth muscle cells is not fully understood.
- Calcium channels are potential pathways for divalent cation entry.
Purpose of the Study:
- To investigate the mechanism of barium-induced contractions in rabbit ear arteries.
- To determine if barium enters smooth muscle cells through calcium channels.
- To assess the role of methoxyverapamil and calcium in modulating barium entry.
Main Methods:
- Isolated perfused rabbit ear artery model.
- Measurement of contractile responses to barium.
- Detection of intracellular barium using specific mitochondrial granules.
- Pharmacological blockade with methoxyverapamil (calcium channel blocker).
- Competitive inhibition studies with calcium.
Main Results:
- Methoxyverapamil abolished barium-evoked contractions.
- Barium entry into smooth muscle cells was confirmed by mitochondrial granule formation.
- Methoxyverapamil prevented the appearance of barium granules.
- Calcium significantly reduced the incidence of barium granules, indicating competitive inhibition.
Conclusions:
- Contractile responses to barium in rabbit ear arteries are mediated by barium entry through calcium channels.
- Methoxyverapamil acts by blocking these calcium channels.
- Calcium competes with barium for entry into vascular smooth muscle cells.
