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Cell-attached single-channel recordings in intact prefrontal cortex pyramidal neurons reveal compartmentalized D1/D5 receptor modulation of the persistent sodium current.

Gorelova N, Seamans JK - Front Neural Circuits (2015)

Bottom Line: While past studies have tested the effects of dopamine on I(Nap), the results have been contradictory largely because of difficulties in measuring I(Nap) using somatic whole-cell recordings.As a result, D1/D5 receptor activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region.By circumventing the pitfalls of previous attempts to study the D1/D5 receptor modulation of I(Nap), we demonstrate conclusively that D1/D5 receptor activation can increase the I(Nap) generated proximally, however questions still remain as to how D1/D5 receptor modulates Na(+) currents in the more distal initial segment where most of the I Nap is normally generated.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Brain Research Centre, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
The persistent Na(+) current (I(Nap)) is believed to be an important target of dopamine modulation in prefrontal cortex (PFC) neurons. While past studies have tested the effects of dopamine on I(Nap), the results have been contradictory largely because of difficulties in measuring I(Nap) using somatic whole-cell recordings. To circumvent these confounds we used the cell-attached patch-clamp technique to record single Na(+) channels from the soma, proximal dendrite (PD) or proximal axon (PA) of intact prefrontal layer V pyramidal neurons. Under baseline conditions, numerous well resolved Na(+) channel openings were recorded that exhibited an extrapolated reversal potential of 73 mV, a slope conductance of 14-19 pS and were blocked by tetrodotoxin (TTX). While similar in most respects, the propensity to exhibit prolonged bursts lasting >40 ms was many fold greater in the axon than the soma or dendrite. Bath application of the D1/D5 receptor agonist SKF81297 shifted the ensemble current activation curve leftward and increased the number of late events recorded from the PD but not the soma or PA. However, the greatest effect was on prolonged bursting where the D1/D5 receptor agonist increased their occurrence 3 fold in the PD and nearly 7 fold in the soma, but not at all in the PA. As a result, D1/D5 receptor activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region. Therefore, D1/D5 receptor modulation appears to be targeted mainly to Na(+) channels in the PD/soma and not the PA. By circumventing the pitfalls of previous attempts to study the D1/D5 receptor modulation of I(Nap), we demonstrate conclusively that D1/D5 receptor activation can increase the I(Nap) generated proximally, however questions still remain as to how D1/D5 receptor modulates Na(+) currents in the more distal initial segment where most of the I Nap is normally generated.

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Related in: MedlinePlus

Quantitative analysis of the late Na+ channel openings. The late channel openings were counted starting 20 ms after the beginning of the depolarizing step. Each panel provides the average group data from PD patches (red diamonds), somatic patches (blue squares) or PA patches (green triangles). The SEM is given by the corresponding colored lines. (A) The number of late Na+ channel openings (per channel, per sweep) (N) (B) dwell time or (C) open probability (Po) of late Na+ channel openings for each region as a function of transmembrane voltage.
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Figure 2: Quantitative analysis of the late Na+ channel openings. The late channel openings were counted starting 20 ms after the beginning of the depolarizing step. Each panel provides the average group data from PD patches (red diamonds), somatic patches (blue squares) or PA patches (green triangles). The SEM is given by the corresponding colored lines. (A) The number of late Na+ channel openings (per channel, per sweep) (N) (B) dwell time or (C) open probability (Po) of late Na+ channel openings for each region as a function of transmembrane voltage.

Mentions: To derive mean values of the number of openings, dwell time and Po we combined data from different patches in 5 mV bins. The mean number of openings, dwell time and Po for events recorded from the three regions are shown in Figure 2. We included in the analysis all late single openings or late openings that appeared as a part of brief bursts. Bursts with durations longer than 40 ms were excluded from this analysis but will be dealt with below. For all regions the largest number of openings was observed at an estimated transmembrane voltage of −30 to −40 mV. The mean number of openings was not significantly different for the three areas (F(2,8) = 0.98, p = 0.41). The mean dwell time progressively increased with larger step voltages and attained an asymptote at ~−20 mV. Again the three regions did not differ in terms of mean dwell time (F(2,8) = 1.77, p = 0.22). Finally the mean Po peaked at ~−30 mV and also did not show a difference between the regions after Holm-Bonferroni correction for multiple comparisons (F(2,8) = 4.3, p = 0.049).


Cell-attached single-channel recordings in intact prefrontal cortex pyramidal neurons reveal compartmentalized D1/D5 receptor modulation of the persistent sodium current.

Gorelova N, Seamans JK - Front Neural Circuits (2015)

Quantitative analysis of the late Na+ channel openings. The late channel openings were counted starting 20 ms after the beginning of the depolarizing step. Each panel provides the average group data from PD patches (red diamonds), somatic patches (blue squares) or PA patches (green triangles). The SEM is given by the corresponding colored lines. (A) The number of late Na+ channel openings (per channel, per sweep) (N) (B) dwell time or (C) open probability (Po) of late Na+ channel openings for each region as a function of transmembrane voltage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325928&req=5

Figure 2: Quantitative analysis of the late Na+ channel openings. The late channel openings were counted starting 20 ms after the beginning of the depolarizing step. Each panel provides the average group data from PD patches (red diamonds), somatic patches (blue squares) or PA patches (green triangles). The SEM is given by the corresponding colored lines. (A) The number of late Na+ channel openings (per channel, per sweep) (N) (B) dwell time or (C) open probability (Po) of late Na+ channel openings for each region as a function of transmembrane voltage.
Mentions: To derive mean values of the number of openings, dwell time and Po we combined data from different patches in 5 mV bins. The mean number of openings, dwell time and Po for events recorded from the three regions are shown in Figure 2. We included in the analysis all late single openings or late openings that appeared as a part of brief bursts. Bursts with durations longer than 40 ms were excluded from this analysis but will be dealt with below. For all regions the largest number of openings was observed at an estimated transmembrane voltage of −30 to −40 mV. The mean number of openings was not significantly different for the three areas (F(2,8) = 0.98, p = 0.41). The mean dwell time progressively increased with larger step voltages and attained an asymptote at ~−20 mV. Again the three regions did not differ in terms of mean dwell time (F(2,8) = 1.77, p = 0.22). Finally the mean Po peaked at ~−30 mV and also did not show a difference between the regions after Holm-Bonferroni correction for multiple comparisons (F(2,8) = 4.3, p = 0.049).

Bottom Line: While past studies have tested the effects of dopamine on I(Nap), the results have been contradictory largely because of difficulties in measuring I(Nap) using somatic whole-cell recordings.As a result, D1/D5 receptor activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region.By circumventing the pitfalls of previous attempts to study the D1/D5 receptor modulation of I(Nap), we demonstrate conclusively that D1/D5 receptor activation can increase the I(Nap) generated proximally, however questions still remain as to how D1/D5 receptor modulates Na(+) currents in the more distal initial segment where most of the I Nap is normally generated.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Brain Research Centre, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
The persistent Na(+) current (I(Nap)) is believed to be an important target of dopamine modulation in prefrontal cortex (PFC) neurons. While past studies have tested the effects of dopamine on I(Nap), the results have been contradictory largely because of difficulties in measuring I(Nap) using somatic whole-cell recordings. To circumvent these confounds we used the cell-attached patch-clamp technique to record single Na(+) channels from the soma, proximal dendrite (PD) or proximal axon (PA) of intact prefrontal layer V pyramidal neurons. Under baseline conditions, numerous well resolved Na(+) channel openings were recorded that exhibited an extrapolated reversal potential of 73 mV, a slope conductance of 14-19 pS and were blocked by tetrodotoxin (TTX). While similar in most respects, the propensity to exhibit prolonged bursts lasting >40 ms was many fold greater in the axon than the soma or dendrite. Bath application of the D1/D5 receptor agonist SKF81297 shifted the ensemble current activation curve leftward and increased the number of late events recorded from the PD but not the soma or PA. However, the greatest effect was on prolonged bursting where the D1/D5 receptor agonist increased their occurrence 3 fold in the PD and nearly 7 fold in the soma, but not at all in the PA. As a result, D1/D5 receptor activation equalized the probability of prolonged burst occurrence across the proximal axosomatodendritic region. Therefore, D1/D5 receptor modulation appears to be targeted mainly to Na(+) channels in the PD/soma and not the PA. By circumventing the pitfalls of previous attempts to study the D1/D5 receptor modulation of I(Nap), we demonstrate conclusively that D1/D5 receptor activation can increase the I(Nap) generated proximally, however questions still remain as to how D1/D5 receptor modulates Na(+) currents in the more distal initial segment where most of the I Nap is normally generated.

Show MeSH
Related in: MedlinePlus