An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones.

Chad, John E.; Eckert, Roger

doi:10.1113/jphysiol.1986.sp016206

Cited by 408 publications

(219 citation statements)

References 56 publications

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“…This is an important consideration in the present experiments since the PKC activators depress Ca currents. However, inclusion of Mg-ATP, EGTA, and the protease inhibitor leupeptin in the whole-cell electrode markedly slows the rate of run-down, as does substitution of Ba for Ca in the extracellular solution (Chad and Eckert, 1986;Kay and Wong, 1987). As can be seen in Figure 64 run-down can be adequately controlled so that drug effects are readily discernible.…”

Section: Efects Of Pkc Activators On Ca Currentsmentioning

confidence: 81%

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Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

1988

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Whole-cell voltage-clamp techniques were used to study the effects of the protein kinase C (PKC) activators phorbol esters and OAG on Ca and K currents in differentiated neurons acutely dissociated from adult hippocampus and in tissue-cultured neurons from fetal hippocampus. PKC activators had selective depressant effects on K currents, with persistent currents (IK and IK-Ca) being reduced and transient current (IA) being unaffected. In both cell types we recorded both high-voltage- activated, noninactivating (L-type) and high-voltage-activated, rapidly inactivating (N-type) Ca current. A low-voltage-activated, rapidly inactivating (T-type) Ca current was also recorded in tissue-cultured neurons but not in acutely dissociated neurons. PKC activators markedly reduced N-type current with less effect on L-type and no effect on T- type Ca current. Effects of PKC activators could be reversed with washing or with application of PKC inhibitors H-7 or polymyxin-B, an effect that could not be attributed to inhibition of cAMP-dependent protein kinase. The Ca/calmodulin inhibitor calmidazolium was ineffective in reversing the actions of PKC activators. Using whole- cell voltage-clamp techniques, we have demonstrated that hippocampal neurons possess 3 distinguishable components of calcium current. Distinct K currents were also observed. Our data strongly support the hypothesis that both Ca and K currents are selectively regulated by PKC and that these effects occur directly on the postsynaptic neuron.

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Section: Efects Of Pkc Activators On Ca Currentsmentioning

confidence: 81%

“…Ca currents are notoriously susceptible to "run-down" during prolonged whole-cell recording (Chad and Eckert, 1986). This is an important consideration in the present experiments since the PKC activators depress Ca currents.…”

Section: Efects Of Pkc Activators On Ca Currentsmentioning

confidence: 94%

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

1988

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“…For the Ca 2+ current of Helix neurons an enzymatic mechanism of Ca-dependent inactivation has been suggested whereby dephosphorylation of the channels by a Ca-dependent phosphatase causes channel inactivation (Chad and Eckert, 1986). If such a mechanism were operative for N channels, differences in the expression of regulatory proteins between cell types might also affect the extent to which Ca-dependent inactivation is observed.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Cox

Dunlap

1994

The Journal of General Physiology

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We have studied the inactivation of high-voltage-activated (HVA), t0-conotoxin-sensitive, N-type Ca 2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca ~+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of ~ 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Cadependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased ~ twofold when the concentration of the Ca 2 § buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca 2 § concentration was raised from 0.5 to 5 mM. (c) Substituting Na § for Ca 2 § as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intraceUular EGTA (10

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“…It has been suggested recently that Ca2+-dependent inactivation of iCa may involve the intermediary action of intracellular Ca2+-binding enzymes that promote protein dephosphorylation (Chad & Eckert, 1986). It is interesting to speculate that (1) similar mechanisms may be present in smooth muscle, (2) the time courses of ica and iB., recorded in various smooth muscles, reflect the relative differences in their Ca2+ current density and subsequent rise in intracellular Ca2+ or Ba2 , (3) these phosphatases may be present in differing concentrations and/or have different affinities for Ca2+ and Ba2+ in various smooth muscles and (4) that receptor-operated modulations of ica may be occurring via these enzymes (Droogmans, Declerck & Casteels, 1987;Pacaud, Loirand, Mironneau & Mironneau, 1987).…”

Section: Voltage-activated Ca2+ Currentmentioning

confidence: 99%

Identification of the major membrane currents in freshly dispersed single smooth muscle cells of guinea‐pig ureter.

Lang

1989

The Journal of Physiology

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SUMMARY1. The passive and active electrical properties of freshly dispersed single cells of the guinea-pig ureter were investigated using standard patch-clamp techniques.2. Action potentials, having a rapid rising phase and a prolonged plateau, were recorded on passing depolarizing currents through the patch pipette when 'nearnormal' physiological gradients were established across the cell membrane (5-9 mM-K+, 1-5 mM-Ca2" in the bath; 126 mM-K' in the pipette).3. Under voltage clamp, depolarization to potentials positive of -50 mV (from a holding potential of -70 or -80 mV) triggered a net inward current which reached a peak in 5-10 ms and then slowly inactivated.4. The averaged membrane current to depolarization to potentials between 30 and 0 mV showed two distinct patterns after the peak of the inward current; the membrane current either moved slowly outward over 400 ms or there was one or more transient outward currents superimposed on the slowly decreasing inward current. Both outward currents were blocked when 5 mM-tetraethylammonium (TEA) was added to the bathing solution, resulting in an increased inward current at all potentials.5. Replacing the extracellular Ca2+ with C02+ (15-5 mM) blocked the inward current and the outward currents to reveal another transient outward current (voltage activated) which activated rapidly to reach a peak within 5 ms and which inactivated exponentially with a time constant of 10 ms. This voltage-activated outward current was inactivated if the membrane was held at -50 mV, but could be reactivated by short hyperpolarizing pre-pulses. The amplitude of this transient current in response to a fixed depolarization (to 0 mV) was half-maximum when the hyperpolarizing pre-pulse was to -66 mV. The voltage-activated outward current was reduced in amplitude when the extracellular potassium was raised to 4;6 mM or upon exposure to 1 mM-4-aminopyridine (4-AP), but was not affected by 5 4M-TEA.

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An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones.

Cited by 408 publications

References 56 publications

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Identification of the major membrane currents in freshly dispersed single smooth muscle cells of guinea‐pig ureter.

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