Roles of A-type potassium currents in tuning spike frequency and integrating synaptic transmission in noradrenergic neurons of the A7 catecholamine cell group in rats.

We investigated voltage-dependent K(+) currents (I(K)) in noradrenergic (NAergic) A7 neurons. The I(K) evoked consisted of A-type I(K) (I(A)), which had the characteristics of a low threshold for activation (approximately -50 mV), fast activation/inactivation, and rapid recovery from inactivation. Since the I(A) were blocked by heteropodatoxin-2 (Hptx-2), a specific Kv4 channel blocker, and the NAergic A7 neurons were shown to be reactive with antibodies against Kv4.1/Kv4.3 channel proteins, we conclude that the I(A) evoked in NAergic neurons are mediated by Kv4.1/Kv4.3 channels. I(A) were also evoked using voltage commands of a single action potential (AP), a subthreshold voltage change between two consecutive APs, or excitatory postsynaptic potential (EPSP) activity recorded in current-clamp mode (CCM). Blockade of the I(A) by 4-AP, a broad spectrum I(A) blocker, or by Hptx-2 increased the half-width and spontaneous firing of APs and reduced the amount of synaptic drive needed to elicit APs in CCM, showing that the I(A) play important roles in regulating the shape and firing frequency of APs and in synaptic integration in NAergic A7 neurons. Since these neurons are the principal projection neurons to the dorsal horn of the spinal cord, these results also suggest roles for Kv4.1/4.3 channels in descending NAergic pain regulation.