1. The Spinal Cord Has an Intrinsic System for the Control of pH
Elham Jalalvand, Brita Robertson, Hervé Tostivint, Peter Wallén, Sten Grillner 
Current Biology 
Volume 26, Issue 10, Pages (May 2016)
DOI: /j.cub
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2. Current Biology 2016 26, 1346-1351DOI: (10.1016/j.cub.2016.03.048)
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3. Figure 1 CSF-c Neurons Respond to Small Deviations in pH
(A) Cross-sectional view of the lamprey spinal cord showing a patched CSF-c neuron with its axonal ramifications into the gray matter and extending to the lateral edge.
(B) In vitro preparation with the central canal (cc) lumen exposed and a CSF-c neuron with a patch pipette. The scale bar represents 10 μm.
(C) Cell-attached recording of a CSF-c neuron responding with an increase of action potential frequency to both acidic and alkaline pH. Synaptic potentials were blocked by gabazine and CNQX/AP5.
(D) Mean action potential frequency during 1 min for each pH condition and normalized to the value at pH 7.4 (% of control).
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4. Figure 2
High and Low pH Induces Inward Current Events in CSF-c Neurons
(A) Whole-cell recording showing spontaneous sodium-mediated action potentials (top trace). Action potentials, as well as GABA- and glutamate-mediated postsynaptic potentials were then blocked by TTX, gabazine, and CNQX/AP5, respectively. Elevating pH to 7.9 resulted in increased frequency and amplitude of depolarizing potentials.
(B) In voltage-clamp mode, only a few current events were seen at pH 7.4, whereas larger and frequent inward current deflections appeared at pH 7.9. APETx2 did not block this response.
(C) Mean frequency increase of events (5–20 pA) in response to elevated pH, remaining after APETx2.
(D) Inward currents at both acidic and alkaline pH in the same cell. Addition of APETx2 only blocked the response to acidic pH.
(E) Both acidic and alkaline pH increased the mean frequency of events. APETx2 blocked the acidic response.
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5. Figure 3
The Response to Elevated pH Is due to Activation of PKD2L1 Channels
(A) Amplitude of inward current events at pH 7.9 increased at hyperpolarized holding potentials and decreased upon depolarization. Synaptic and action potentials were blocked by application of gabazine, CNQX/AP5, and TTX.
(B) Inward current responses to increased pH reversed at approximately 0 mV.
(C) Unitary current deflections, recorded at elevated pH (7.9).
(D and E) In situ hybridization images showing laterally located CSF-c neurons coexpressing the PKD2L1 channel and somatostatin (arrows in E). (E) Confocal single optical section is shown (<1 μm). The scale bars represent 100 μm (D) and 10 μm (E).
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6. Figure 4 Elevated pH Reduces the Locomotor Rhythm
(A) Illustration of ventral root recordings with suction electrodes in the intact, isolated spinal cord preparation (VR-L and VR-R, left and right ventral root, respectively).
(B) Alternating burst activity during NMDA-induced fictive locomotion at control conditions (pH 7.4), pH 7.9, and in the presence of the ASIC3 blocker APETx2.
(C) Elevated pH significantly prolonged the cycle period. APETx2 did not block this suppressing effect.
(D) Locomotor activity during control conditions (pH 7.4), pH 7.9, and following application of the somatostatin receptor antagonist CYN
(E) Application of CYN led to a shortening of the period length at pH 7.4. In the presence of the antagonist, pH 7.9 had no effect on the cycle period.
(F) Small deviations from pH 7.4 reduce the locomotor burst rate (black curve), with a clear decrease at both acidic and alkaline pH. Gray curve indicates the effect of pH on CSF-c neuron firing, with a steep increase in action potential frequency at both acidic and alkaline pH.
(G) Deviations from pH 7.4 activate ASIC3 and PKD2L1 in CSF-c neurons, suppressing the spinal locomotor network.
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