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Divalent cation dependent inactivation of the high-voltage-activated Ca-channel current in chick sensory neurons
Abstract:
We have used the whole-cell clamp technique to investigate inactivation of the omega-conotoxin sensitive high-voltage-activated Ca-channel current (HVA current [2]) carried either by Ca, Ba or Sr (2.5 mM) in chick sensory neurons. At a low internal EGTA concentration (0.1 mM), Ca-channel currents clearly inactivated irrespective of the species of divalent cation carrying the current. During 150 ms pulses, current inactivated to 0.57, 0.67 and 0.75 of the peak current in Ca, Ba and Sr solution, respectively. Time constants of inactivation (26 +/- 10 ms and 280 +/- 50 ms, mean +/- S.D., in Ba) were largely independent of the membrane potential. Double-pulse experiments showed that the amount of inactivation left by a pre-pulse was proportional to the amplitude of the current evoked by the pre-pulse. No inactivation was induced by an outward current elicited by a strong depolarization to +60 mV. With an internal EGTA concentration of 20 mM, the amount of inactivation was significantly smaller. In conclusion, the inactivation of the HVA Ca-channel currents during current flow depends mostly on the entry of divalent cations irrespective of their species.
Insights
Calcium channel currents inactivate similarly regardless of the ion carrying them. This inactivation of high-voltage-activated calcium channels depends on divalent cation entry, not their specific type.
Area of Science:
- Neuroscience
- Cell Physiology
Background:
- High-voltage-activated calcium channels (HVA) are crucial for neuronal function.
- Omega-conotoxin sensitive HVA channels mediate significant calcium currents.
- Understanding HVA current inactivation is key to deciphering neuronal excitability.
Purpose of the Study:
- To investigate the inactivation properties of omega-conotoxin sensitive HVA calcium channels.
- To determine if the species of divalent cation (Ca, Ba, Sr) affects HVA current inactivation.
- To explore the dependence of HVA current inactivation on intracellular calcium concentration.
Main Methods:
- Whole-cell clamp technique applied to chick sensory neurons.
- Ionic currents carried by Ca2+, Ba2+, or Sr2+ were measured.
- Inactivation was studied using voltage pulses and double-pulse protocols.
- Varying internal EGTA concentrations modulated intracellular divalent ion levels.
Main Results:
- HVA currents inactivated significantly with Ca2+, Ba2+, or Sr2+ at low internal EGTA (0.1 mM).
- Inactivation levels were comparable across different divalent cations (0.57-0.75 of peak current).
- Inactivation magnitude correlated with the amplitude of the preceding current pulse.
- Higher internal EGTA (20 mM) reduced the extent of inactivation.
Conclusions:
- Inactivation of HVA calcium channel currents is primarily driven by the influx of divalent cations.
- The specific species of divalent cation does not significantly alter the inactivation process.
- Intracellular buffering capacity influences the degree of HVA current inactivation.