The hyperpolarization-induced suppression of subsequent buy Trichostatin A firing was blocked by internal TEA and by external α-dendrotoxin (Figure 6 and Figure 7). Furthermore, somatic membrane patches showed characteristic properties of a KDR current (activation at ∼−25 mV) and steady-state inactivation at Vrest could be removed by hyperpolarization (Figure 8). The collected results support a KDR mechanism whereby hyperpolarizations from Vrest increase the available KDR channel pool and suppress firing during subsequent depolarization. The study of intrinsic mechanisms for adaptation in intact cells and circuits is challenging and requires complementary experimental approaches. Some of these approaches

yielded unexpected results worth mentioning. For example, external α-dendrotoxin increased firing significantly, whereas internal TEA (20 mM) did not (Figure 6 and Figure 7), even though TEA is a more general blocker of K channels. However,

TEA increased the spike width substantially. The increased spike width increases the time that unblocked K channels could be activated and also possibly leads to increased Na channel inactivation. Thus, unintended effects on K and Na channels may have counteracted any increase in firing rate caused by specifically blocking α-dendrotoxin-sensitive KDR channels. Another unexpected result was that hyperpolarizing current had no effect on subsequent firing to weak visual stimulation but enhanced slightly the firing to weak current injection (Figure 3). The distinct effects may be explained click here by the different time courses of the stimuli: the current injection was a square-pulse, whereas the low-contrast synaptic input was necessarily more sluggish due to the filtering by retinal circuitry. However, in general, similar results were

elicited by protocols that used either current injection or synaptic stimulation as the test stimulus (Figure 1, Figure 2 and Figure 4). Somatic membrane patch recordings showed several properties of KDR currents that could explain their role in contrast adaptation. First, the channels activate at voltages traversed during an action potential (activation at −25 mV). Second, channel inactivation at Vrest could be removed by hyperpolarization (Figure 8). Thus, a period of Mirabegron hyperpolarization would increase the number of available channels, which could then be activated during a subsequent burst of firing. The initial spikes in the burst would be largely unaffected, but channels opened during these initial spikes would suppress subsequent spikes (Figure 2) because KDR deactivation is relatively slow (Figure 8D) compared to the typical interspike interval during the initial spike burst (Figure 1); Kv1 channels also contribute to the interspike interval in neocortical pyramidal cells (Guan et al., 2007).