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. 2006 Aug 21:2:28.
doi: 10.1186/1744-8069-2-28.

Ionic basis of a mechanotransduction current in adult rat dorsal root ganglion neurons

Gordon C McCarter  1 , Jon D Levine
Affiliations

Ionic basis of a mechanotransduction current in adult rat dorsal root ganglion neurons

Gordon C McCarter et al. Mol Pain. .

Abstract

Sensory mechanical transduction - necessary for hearing, proprioception, and the senses of touch and pain - remains poorly understood. In somatosensation, even the basic properties of the mechanically sensitive excitatory ionic currents that are assumed to mediate mechanical transduction are largely undescribed. We have recorded, from the soma of rat dorsal root ganglion (DRG) neurons in vitro, whole-cell ionic currents induced by the impact of a piezo-electrically driven glass probe. This transient mechanically activated current was observed in virtually all DRG neurons tested. In ion substitution experiments the current could be carried nonselectively by most cations, including divalent and organic cations, but not by chloride or sulfate ions. In addition, the mechanically activated current carried by monovalent cations was consistently blocked by millimolar concentrations of external calcium or magnesium. Based on these results, the transient mechanical transduction current observed in somatosensory neurons in vitro is mediated by large-pore mechanically gated channels nonselective for cations but impermeable to anions.

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Figures

Figure 1
Figure 1
Mechanical stimulus elicits fast transient currents in most DRG neurons. (A) Representative traces of currents in a typical neuron (36-μm diameter) in response to a transient and a sustained mechanical stimulus at -70 mV. The travel of the probe is shown at top, returning to start position immediately for one stimulus and remaining in contact with the neuron for 200 ms for the other. The probe travelled 33 μm; therefore its velocity was 3.3 mm/s. Both responses displayed an identical initial fast component but when the neuron was transiently stimulated the current inactivated within 4 ms, while the sustained stimulus elicited additional later components – possibly induced by residual vibration of the probe – that were completely inactivated within ~75 ms. The electrode contained the potassium-based electrode solution. (B) Largest current amplitude recorded from a series of DRG neurons plotted against the cell soma diameter. Each point represents the largest current evoked from a single neuron at -70 mV using electrodes filled with either a potassium- (○) or cesium-based (△) electrode solution. All cells from 35 preparations (n = 133) in which a stable recording could be maintained through the initial mechanical stimulation are included. Setting the threshold for a response at 1 pA/pF, 98% of the DRG neurons tested expressed the MA current. Solid and dashed lines represent a linear regression of the data for cells recorded using electrodes filled with potassium- and cesium-based electrode solution, respectively.
Figure 2
Figure 2
The mechanically activated current is a non-selective cation current. (A) Representative traces of mechanotransduction currents evoked by identical mechanical stimuli (probe velocity 4.3 mm/s) from a DRG neuron with a soma diameter of 36 μm. Membrane potential was stepped for 1 s to voltages ranging from -110 to +130 mV in steps of 20 mV, 720 ms prior to mechanical stimulation. Every other trace is omitted for clarity. (B) Mean amplitudes of currents evoked by mechanical stimulation of DRG neurons (n = 20) bathed in the normal external solution and using cesium sulfate/cesium chloride electrode solution. The mean amplitude at -70 mV was -436 ± 145 pA and the mean reversal potential was 25 ± 4 mV. (C) Comparison of I-V data for the 4 smallest (<35 μm, closed squares) and 6 largest (>40 μm, open squares) diameter DRG neurons in standard solutions. The two curves are not significantly different from each other, using a 2-way ANOVA test. (D) Mean amplitudes of currents evoked by mechanical stimulation of DRG neurons in the normal external bath solution while using electrodes filled with cesium and the impermeant anion methanesulfonate (n = 6). The mean reversal potential was 23 ± 5 mV.
Figure 3
Figure 3
The mechanotransduction current can be carried by monovalent ions. (A) Mechanically activated current traces recorded from a DRG neuronal soma with a diameter of 38 μm when external solution consisted of 140 mM NaCl (with HEPES, glucose, and sucrose). Traces shown are for membrane voltages clamped at levels from -110 to +130 mV in increments of 40 mV. Probe velocity was 3.5 mm/s. (B) Mean peak current-voltage relation in sodium chloride bath solution (closed circles). The mean amplitude of peak current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (C) Current traces recorded from another neuron (41-μm diameter) in LiCl bath solution. Traces shown were recorded at command voltages of -111 to +89 mV in increments of 40 mV. Probe velocity was 3.5 mm/s. (D) Mean current-voltage relation in lithium chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (E) Current traces recorded from a 37-μm-diameter DRG neuron when bath solution consisted of 140 mM KCl (with HEPES, glucose, and sucrose) at membrane voltages stepped from -109 to +91 mV in increments of 40 mV. Probe velocity was 4.1 mm/s. (F) Mean current-voltage relation in potassium chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (G) Current traces recorded from a neuron (40-μm diameter) in cesium chloride bath with the membrane voltage clamped at -108 to +92 mV in increments of 40 mV. Probe velocity was 3.8 mm/s. (H) Mean current-voltage relation for MA currents in cesium chloride bath and using the potassium-based electrode solution (closed circles). The mean amplitude of current seen with the standard external solution at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle.
Figure 4
Figure 4
The mechanotransduction current can be carried and blocked by calcium and magnesium ions. (A) Mechanically activated current traces recorded from a 40-μm DRG neuronal soma when bath solution consisted of 100 mM CaCl2 (with HEPES, glucose, and sucrose) at membrane voltages of -112, -72, -32, +48, and +88 mV. Probe velocity was 3.4 mm/s. (B) Mean current-voltage relation in calcium chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (C) Current traces recorded from a neuron (41-μm diameter) when bathed in 100 mM MgCl2 at membrane voltages ranging from -112 to +128 mV in steps of 40 mV. Probe velocity was 3.5 mm s-1. (D) Mean current-voltage relation for mechanotransduction currents in magnesium chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (E) Amplitudes of mechanically activated current responses at -70 mV in otherwise standard external solution containing CaCl2 concentrations of 0.025 mM, 0.25 mM, 2.5 mM (standard), and 25 mM and no added MgCl2. All current amplitudes were normalized to the size of the current in the same cell (n = 6–8 cells) using the same stimulus parameters in the standard bath solution with 2.5 mM CaCl2 and 0.6 mM MgCl2 at -70 mV. (F) Amplitudes of responses at -70 mV in bath solutions all containing 0.025 mM CaCl2 but with MgCl2 concentrations of 0.06 mM, 0.6 mM (standard), and 6 mM. At the left is the value from panel E for 0.025 mM CaCl2 and 0 MgCl2 for reference. All current amplitudes were normalized to the size of the current in the same cell (n = 3–5 cells) using the same stimulus parameters in the standard bath solution with 2.5 mM CaCl2 and 0.6 mM MgCl2 at -70 mV.
Figure 5
Figure 5
The mechanotransduction current can be carried by organic ions. (A) Mechanically activated current traces recorded from a DRG neuron (48-μm diameter) when bath solution consisted of 140 mM choline chloride at membrane voltages stepped from -111 to +89 mV in increments of 40 mV. (B) Mean current-voltage relation in choline chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle. (C) Current traces recorded from a 35-μm neuron when bathed in 140 mM NMDG-Cl with membrane voltage clamped at -112 to +88 mV in increments of 40 mV. Probe velocity was 3.9 mm/s. (D) Mean current-voltage relation for mechanotransduction currents in N-mtheyl-D-glucamine chloride bath (closed circles). The mean amplitude of current seen in standard solutions at -70 mV, in the same cells using the same stimulus parameters, is indicated by the open circle.
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