Figure 3.
Glycolytic inhibition hyperpolarizes the membrane potential by decreasing a constitutively active conductance. A, Action potentials were recorded immediately after establishing a whole-cell recording from control (Ctrl) neurons or neurons preincubated in IAA (1 mm) and βHB (2.5 mm). Representative traces from two separate neurons, one in the control condition (black line) and one preincubated in IAA and βHB (blue line), show that IAA increases interspike intervals. B, The action potential waveform of neurons incubated in IAA in the presence of βHB (n = 7; blue trace) was similar to action potentials from control neurons (n = 5; black trace) but did have a more prominent afterhyperpolarization (calibration: 20 mV, 5 ms). C, With action potentials blocked using lidocaine (1 mm) and with the KATP channel blocker Glib (200 nm) present, application of IAA (1 mm) in the continued presence of βHB (2.5 mm) decreased the membrane potential of SNr neurons recorded in perforated-patch configuration (−53.8 ± 2.0 to −67.5 ± 1.3 mV; n = 8; p = 3.0 × 10−5, Student's paired t test). D, Perforated-patch voltage-clamp recordings (holding potential of −70 mV) of SNr neurons in the presence of lidocaine (1 mm) exhibited a decrease in inward current after application of IAA (1 mm) with βHB (2.5 mm; −41.9 ± 7.4 to −6.1 ± 3.7 pA; n = 4; p = 0.0009, Student's paired t test). All error bars indicate SEM; *p < 0.05.