Potassium channels play a critical role in regulating many aspects of action potential firing. To establish the contribution of the voltage-dependent potassium channel Kv1.1 in regulating excitability, we used the selective blocker, dendrotoxin-K (DTX-K) and siRNA targeted to Kv1.1 to determine their effects on action potential (AP) firing in small diameter capsaicin-sensitive sensory neurons. A 5 min exposure to 10 nM DTX-K suppressed the total potassium current (IK) measured at +60 mV by approximately 33%. DTX-K produced a two-fold increase in the number of APs evoked by a ramp of depolarizing current. Associated with increased firing was a decrease in firing threshold and rheobase. A 48 hr treatment with siRNA targeted to Kv1.1 reduced the expression of this channel protein by ~60% as measured in western blots. After treatment with siRNA, IK was no longer sensitive to DTX-K, indicating a loss of functional protein. Similarly, after siRNA treatment exposure to DTX-K had no affect on the number of evoked APs, firing threshold, or rheobase. However, after siRNA treatment, the firing thresholds had values that were similar to those obtained after acute exposure to DTX-K, suggesting that the loss of Kv1.1 plays a critical role in setting this parameter of excitability. These results demonstrate that Kv1.1 plays an important role in limiting AP firing and that siRNA may be a useful approach to establish the role of specific ion channels in the absence of selective antagonists.