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• W2033375071 abstract "The Mg 2+ block of Na + and Ca 2+ currents through high‐voltage activated (HVA; L‐ and N‐type) Ca 2+ channels was studied in chick dorsal root ganglion neurones. In low extracellular [Ca 2+ ] (< 10 −8 M) and with Na o + and Cs i + as the main charge carriers (120 m m ), HVA Na + currents started to activate at −40 mV, reached inward peak values near 0 mV and reversed at about +40 mV. Addition of 30–500 μ m Mg 2+ to the bath caused a strong depression of inward Na + currents that was voltage and dose dependent ( K D =39 μ m in 120 m m Na + at −10 mV). The block was maximal at negative potentials (< −70 mV) and decreased with increasing positive potentials, suggesting that Mg 2+ cannot escape to the cell interior. Block of Ca 2+ currents by Mg 2+ was also voltage dependent, but by three orders of magnitude less potent than with Na + currents ( K D = 24 m m in 2 m m Ca 2+ at −30 mV). The high concentration of Mg 2+ caused a prominent voltage shift of channel gating kinetics induced by surface charge screening effects. To compensate for this, Mg 2+ block of inward Ca 2+ currents was estimated from the instantaneous I–V relationships on return from very positive potentials (+100 mV). Inward Na + and Ca 2+ tail currents following depolarization to +90 mV were markedly depressed, suggesting that channels cleared of Mg 2+ ions during strong depolarization are quickly re‐blocked on return to negative potentials. The kinetics of re‐block by Mg 2+ was too fast (< 100 μs) to be resolved by our recording apparatus. This implies a rate of entry for Mg 2+ > 1.45 × 10 8 M − s −1 when Na + is the permeating ion and a rate approximately 3 orders of magnitude smaller for Ca 2+ . Mg 2+ unblock of HVA Na + currents at +100 mV was independent of the size of outward currents, whether Na + , Cs + or NMG + were the main internal cations. Consistent with the idea of a high‐affinity binding site for Ca 2+ inside the channel, micromolar amounts of Ca 2+ caused a strong depression of Na + currents between −40 and 0 mV, which was effectively relieved with more positive as well as with negative potentials ( K D = 0.7μ m in 120 m m Na + at −20 mV). In this case, the kinetics of re‐block could be resolved and gave rates of entry and exit for Ca 2+ of 1.4 × 10 8 M −1 s −1 and 2.95 × 10 2 s −1 , respectively. The strong voltage dependence and weak current dependence of HVA channel block by divalent cations and the markedly different K D values of Na + and Ca 2+ current block by Mg 2+ can be well described by a previously proposed model for Ca 2+ channel permeation based on interactions between the permeating ion and the negative charges forming the high‐affinity binding site for Ca 2+ inside the pore ( Lux, Carbone & Zucker, 1990 )." @default.
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• W2033375071 date "1997-10-01" @default.
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• W2033375071 title "Ca²⁺and Na⁺permeability of high-threshold Ca²⁺channels and their volt age-dependent block by Mg²⁺ions in chick sensory neurones" @default.
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• W2033375071 doi "https://doi.org/10.1111/j.1469-7793.1997.001bf.x" @default.
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