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Cell type-specific effects of adenosine on cortical neurons.

van Aerde KI, Qi G, Feldmeyer D - Cereb. Cortex (2013)

Bottom Line: Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date.We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location.These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening.

View Article: PubMed Central - PubMed

Affiliation: Forschungszentrum Jülich, Institute of Neuroscience and Medicine, INM-2, D-52425 Jülich, Germany Current address: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Science, 1105 BA Amsterdam, The Netherlands.

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Adenosine hyperpolarizes the membrane potential of L5 pyramidal cells through the adenosine A1 receptor. (A) Example traces of the RMP during bath application of 100 μM adenosine (start at arrow). Average response is shown in black (n = 34). (B) Example dose–response plot (inset) and average responses for adenosine concentrations from 1 to 200 μM (n = 6). (C) Example trace (left) and average response (right, n = 4) of the RMP during application of 1 μM adenosine A1 receptor agonist CPA. (D) Example trace (left) and average response (right, n = 3) of the RMP during application of 100 μM adenosine, followed by coapplication of 1 μM the A1R antagonist CPT. (E) Example IV plot during the absence (control) and presence of adenosine. Adenosine induced an outward current with a reversal potential of −99.8 mV. (F) Example trace (left) and average responses (right, n = 6) from L5 pyramidal neurons held at −60 mV in whole-cell voltage-clamp configuration during application of 100 μM adenosine, in the absence (left, control) or presence of 200 μM Ba2+. (G) Example traces and average responses (right, n = 6) from L5 pyramidal neurons held at varying hyperpolarizing holding potentials (−60 to −120 mV) to measure the Ih current before (left) and during (middle) application of 100 μM adenosine. Note that experiments were performed in the presence of 200 μM Barium. (H) Left, firing rate as a function of injected current before (circles) and after (triangles) adenosine application. Note that the current is normalized to the rheobase current of the control condition. Right, slope of the firing rate as a function of current plotted against rheobase. Rheobase current was calculated from 10 pA current steps. Averages for the control (circles) and adenosine (triangles) condition are shown with error bars. *P < 0.05, **P < 0.01.
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BHT274F1: Adenosine hyperpolarizes the membrane potential of L5 pyramidal cells through the adenosine A1 receptor. (A) Example traces of the RMP during bath application of 100 μM adenosine (start at arrow). Average response is shown in black (n = 34). (B) Example dose–response plot (inset) and average responses for adenosine concentrations from 1 to 200 μM (n = 6). (C) Example trace (left) and average response (right, n = 4) of the RMP during application of 1 μM adenosine A1 receptor agonist CPA. (D) Example trace (left) and average response (right, n = 3) of the RMP during application of 100 μM adenosine, followed by coapplication of 1 μM the A1R antagonist CPT. (E) Example IV plot during the absence (control) and presence of adenosine. Adenosine induced an outward current with a reversal potential of −99.8 mV. (F) Example trace (left) and average responses (right, n = 6) from L5 pyramidal neurons held at −60 mV in whole-cell voltage-clamp configuration during application of 100 μM adenosine, in the absence (left, control) or presence of 200 μM Ba2+. (G) Example traces and average responses (right, n = 6) from L5 pyramidal neurons held at varying hyperpolarizing holding potentials (−60 to −120 mV) to measure the Ih current before (left) and during (middle) application of 100 μM adenosine. Note that experiments were performed in the presence of 200 μM Barium. (H) Left, firing rate as a function of injected current before (circles) and after (triangles) adenosine application. Note that the current is normalized to the rheobase current of the control condition. Right, slope of the firing rate as a function of current plotted against rheobase. Rheobase current was calculated from 10 pA current steps. Averages for the control (circles) and adenosine (triangles) condition are shown with error bars. *P < 0.05, **P < 0.01.

Mentions: To verify if adenosine acts mainly through the adenosine A1 receptor in the mPFC, we first made recordings from L5 pyramidal neurons and bath-applied adenosine and A1 specific agonists and antagonists. Bath application of 100 μM adenosine led on average to a 3.8 ± 0.3 mV hyperpolarization of the RMP of L5 pyramidal neurons (n = 30; Fig. 1A and Table 1). The size of the hyperpolarization was dependent on the adenosine concentration (Fig. 1B, EC50 18.6 ± 4.3 μM, n = 8), but bath application of 5 μM adenosine already caused a significant hyperpolarization [Fig. 1B, RMP: −66.1 ± 1.2 mV (control), −67.3 ± 1.2 mV (5 μM adenosine), difference −1.2 ± 0.4 mV, n = 10, paired t-test P < 0.01]. The effect of adenosine could be mimicked by bath application of 1 μM CPA, a specific agonist of the adenosine A1 receptor [Fig. 1C, RMP: −64.1 ± 1.3 mV (control), −67.9 ± 1.0 mV (CPA), difference −3.8 ± 0.6 mV, n = 4, paired t-test P < 0.01]. In addition, bath application of the adenosine A1 receptor antagonist CPT reversed the adenosine-induced hyperpolarization to baseline levels [Fig. 1D, RMP: −64.6 ± 3.0 mV (control), −66.6 ± 3.4 mV (adenosine), −64.7 ± 3.2 mV (adenosine + 1 μM CPT), n = 3, paired t-test P < 0.05].Table 1


Cell type-specific effects of adenosine on cortical neurons.

van Aerde KI, Qi G, Feldmeyer D - Cereb. Cortex (2013)

Adenosine hyperpolarizes the membrane potential of L5 pyramidal cells through the adenosine A1 receptor. (A) Example traces of the RMP during bath application of 100 μM adenosine (start at arrow). Average response is shown in black (n = 34). (B) Example dose–response plot (inset) and average responses for adenosine concentrations from 1 to 200 μM (n = 6). (C) Example trace (left) and average response (right, n = 4) of the RMP during application of 1 μM adenosine A1 receptor agonist CPA. (D) Example trace (left) and average response (right, n = 3) of the RMP during application of 100 μM adenosine, followed by coapplication of 1 μM the A1R antagonist CPT. (E) Example IV plot during the absence (control) and presence of adenosine. Adenosine induced an outward current with a reversal potential of −99.8 mV. (F) Example trace (left) and average responses (right, n = 6) from L5 pyramidal neurons held at −60 mV in whole-cell voltage-clamp configuration during application of 100 μM adenosine, in the absence (left, control) or presence of 200 μM Ba2+. (G) Example traces and average responses (right, n = 6) from L5 pyramidal neurons held at varying hyperpolarizing holding potentials (−60 to −120 mV) to measure the Ih current before (left) and during (middle) application of 100 μM adenosine. Note that experiments were performed in the presence of 200 μM Barium. (H) Left, firing rate as a function of injected current before (circles) and after (triangles) adenosine application. Note that the current is normalized to the rheobase current of the control condition. Right, slope of the firing rate as a function of current plotted against rheobase. Rheobase current was calculated from 10 pA current steps. Averages for the control (circles) and adenosine (triangles) condition are shown with error bars. *P < 0.05, **P < 0.01.
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BHT274F1: Adenosine hyperpolarizes the membrane potential of L5 pyramidal cells through the adenosine A1 receptor. (A) Example traces of the RMP during bath application of 100 μM adenosine (start at arrow). Average response is shown in black (n = 34). (B) Example dose–response plot (inset) and average responses for adenosine concentrations from 1 to 200 μM (n = 6). (C) Example trace (left) and average response (right, n = 4) of the RMP during application of 1 μM adenosine A1 receptor agonist CPA. (D) Example trace (left) and average response (right, n = 3) of the RMP during application of 100 μM adenosine, followed by coapplication of 1 μM the A1R antagonist CPT. (E) Example IV plot during the absence (control) and presence of adenosine. Adenosine induced an outward current with a reversal potential of −99.8 mV. (F) Example trace (left) and average responses (right, n = 6) from L5 pyramidal neurons held at −60 mV in whole-cell voltage-clamp configuration during application of 100 μM adenosine, in the absence (left, control) or presence of 200 μM Ba2+. (G) Example traces and average responses (right, n = 6) from L5 pyramidal neurons held at varying hyperpolarizing holding potentials (−60 to −120 mV) to measure the Ih current before (left) and during (middle) application of 100 μM adenosine. Note that experiments were performed in the presence of 200 μM Barium. (H) Left, firing rate as a function of injected current before (circles) and after (triangles) adenosine application. Note that the current is normalized to the rheobase current of the control condition. Right, slope of the firing rate as a function of current plotted against rheobase. Rheobase current was calculated from 10 pA current steps. Averages for the control (circles) and adenosine (triangles) condition are shown with error bars. *P < 0.05, **P < 0.01.
Mentions: To verify if adenosine acts mainly through the adenosine A1 receptor in the mPFC, we first made recordings from L5 pyramidal neurons and bath-applied adenosine and A1 specific agonists and antagonists. Bath application of 100 μM adenosine led on average to a 3.8 ± 0.3 mV hyperpolarization of the RMP of L5 pyramidal neurons (n = 30; Fig. 1A and Table 1). The size of the hyperpolarization was dependent on the adenosine concentration (Fig. 1B, EC50 18.6 ± 4.3 μM, n = 8), but bath application of 5 μM adenosine already caused a significant hyperpolarization [Fig. 1B, RMP: −66.1 ± 1.2 mV (control), −67.3 ± 1.2 mV (5 μM adenosine), difference −1.2 ± 0.4 mV, n = 10, paired t-test P < 0.01]. The effect of adenosine could be mimicked by bath application of 1 μM CPA, a specific agonist of the adenosine A1 receptor [Fig. 1C, RMP: −64.1 ± 1.3 mV (control), −67.9 ± 1.0 mV (CPA), difference −3.8 ± 0.6 mV, n = 4, paired t-test P < 0.01]. In addition, bath application of the adenosine A1 receptor antagonist CPT reversed the adenosine-induced hyperpolarization to baseline levels [Fig. 1D, RMP: −64.6 ± 3.0 mV (control), −66.6 ± 3.4 mV (adenosine), −64.7 ± 3.2 mV (adenosine + 1 μM CPT), n = 3, paired t-test P < 0.05].Table 1

Bottom Line: Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date.We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location.These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening.

View Article: PubMed Central - PubMed

Affiliation: Forschungszentrum Jülich, Institute of Neuroscience and Medicine, INM-2, D-52425 Jülich, Germany Current address: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Science, 1105 BA Amsterdam, The Netherlands.

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Related in: MedlinePlus