Nociceptive Neurons Differentially Express Fast and Slow T-Type Ca2+ Currents in Different Types of Diabetic Neuropathy
Figure 1
NTCN neurons express both fast and slow T-currents. (a) Identification of NTCN neurons. (A) A typical fluorescent image of an IB4-positive small-size DRG neuron. Note the intensive fluorescent ring associated with the neuronal plasma membrane. Scale bar, 20 μm. (B) A typical trace of transmembrane current induced by application of capsaicin (2 μM) in IB4-positive small-sized DRG neuron. IB4-positive capsaicin-sensitive small size DRG neurons were further considered as nonpeptidergic thermal C-type nociceptive (NTCN) neurons. (b) Representative current traces illustrate expression of T-currents with fast and slow kinetics of inactivation in different NTCN neurons. Currents were elicited using a 0.5 s voltage step to −45 mV after preconditioning at −95 mV for 3 s. A grey inset shows the same currents normalized by amplitude to underline a difference in kinetics of current inactivation. (c) A histogram demonstrates a pooled distribution of inactivation time constants of T-currents recorded from 85 neurons of control and PDN groups. The time constants were calculated from a single-exponential fit of current decay. A smooth curve is a fit of the distribution by a sum of two Gaussians. According to this fit T-currents were divided into fast ( ms; white bars) and slow ( ms; black bars) subtypes. (d) Kinetics of inactivation of fast and slow T-currents in control and PDN groups. Each column is the mean and SEM from the number of neurons specified in Figure 2(a). No significant difference compared to control was revealed under PDN conditions in kinetics of inactivation for both fast and slow T-currents. (e) Peak current density (PCD) of fast and slow T-currents under the control conditions. The columns are the mean and SEM calculated from 31 fast and 12 slow T-currents. ***. (f) PCD plotted versus inactivation time constant for fast and slow T-currents recorded under the control conditions. No significant correlations were found for both current types indicating that the difference in inactivation between fast and slow T-currents was not due to voltage clamp problems. Lines were liner fits of the dependencies; as a measure of correlation is shown in the plot.
