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Properties of the leakage current pathway: effects of the gadolinium ion on myelinated axons
Abstract:
Voltage-clamp experiments on myelinated axons revealed that the trivalent gadoliniumion ion blocked the leakage current in a dose-dependent manner. The block showed 1:2 stoichiometry, and 50% reduction at 700 microM. Na+ and K+ currents were blocked at ten times lower concentration and showed 1:1 stoichiometry. Comparisons with biochemical studies suggest that the leakage current directly depends on a phospholipid pathway in contrast to the protein-channel dependent Na+ and K+ currents. The results may be explained by a leakage current pathway located at the interface between channel proteins and the lipid phase.
Insights
Gadolinium ions selectively block axonal leakage currents, suggesting a phospholipid pathway distinct from protein-based sodium and potassium channels. This finding offers insights into ion transport mechanisms at the lipid-protein interface.
Area of Science:
- Neuroscience
- Biophysics
- Cellular Physiology
Background:
- Myelinated axons exhibit leakage currents distinct from voltage-gated sodium (Na+) and potassium (K+) currents.
- Understanding the molecular basis of these currents is crucial for comprehending axonal function and dysfunction.
Purpose of the Study:
- To investigate the ionic basis and molecular correlates of the leakage current in myelinated axons.
- To differentiate the pathway of leakage current from Na+ and K+ currents using gadolinium ion as a blocker.
Main Methods:
- Voltage-clamp electrophysiology was employed on myelinated axons.
- Dose-dependent block and stoichiometry of gadolinium ion on different currents were analyzed.
- Biochemical studies were compared to interpret the results.
Main Results:
- Trivalent gadolinium ions blocked leakage current in a dose-dependent manner with 1:2 stoichiometry, showing 50% reduction at 700 microM.
- Na+ and K+ currents were blocked at ten times lower concentrations with 1:1 stoichiometry.
- Leakage current appears to depend on a phospholipid pathway, unlike protein-channel dependent Na+ and K+ currents.
Conclusions:
- The results suggest a distinct pathway for leakage current, potentially located at the lipid-protein interface of the axonal membrane.
- This pathway is independent of the protein channels responsible for Na+ and K+ currents.
- Gadolinium ion serves as a valuable tool for distinguishing between different ionic pathways in excitable cells.