Figure S5.
Part A shows representative whole-cell H C N current traces recorded from a D R G neuron in the presence of 0.5 millimolar c A M P. The black traces (left) show the Before state with a tau 1 equals105 milliseconds, while the blue traces (right) show the state After m beta C D with a faster tau 1 equals 57 milliseconds. The traces indicate a visible acceleration in the rate of channel activation following cholesterol depletion. Part B presents a graph measuring the primary time constant of channel activation (tau 1) at hyperpolarizing voltages from minus 100 millivolts to minus 130 millivolts. The vertical axis represents tau 1 activation in milliseconds, ranging from 0 to 350. Two data lines are shown: red (Before) and blue (After m beta C D). The blue line sits consistently below the red line, illustrating that cholesterol depletion significantly decreases the time constant, thereby speeding up channel activation across all tested voltages. All values are approximate.
Increase in current amplitude and acceleration of the HCN channel activation by cholesterol depletion in the presence of a saturating concentration of cAMP. (A) Representative whole-cell HCN current traces recorded from naïve nociceptor DRG neurons in the presence of the added 0.5 mM cAMP in the patch-clamp pipette solution. Current amplitude increased, and the kinetics of channel activation were faster. (B) Measured primary time constant of channel activation at different hyperpolarizing voltages from the same patch in the panel A.