The voltage dependence of inactivation showed two components, consistent with the presence of at least two

channel types (Figure 8F, green line). The rate of inactivation was high between −120 and −60 mV and again between −35 and −10 mV. Thus, a component of inactivation can selleck chemicals llc be removed by hyperpolarization from Vrest. The collected pharmacology and somatic patch recordings suggest that a Kv1-family KDR channel mediates the suppressive effect of hyperpolarization on subsequent depolarization and firing in retinal ganglion cells and thereby contributes to an intrinsic mechanism for contrast adaptation. The contrast adaptation observed in ganglion cell firing exceeds that present in the subthreshold Vm or excitatory membrane currents (Kim and Rieke, 2001, Zaghloul et al., 2005, Beaudoin et al., 2007 and Beaudoin et al., 2008). This discrepancy implicates intrinsic mechanisms for adaptation within ganglion cells (Gaudry and Reinagel, 2007b). Here, we demonstrate two distinct intrinsic mechanisms for

contrast adaptation in the OFF Alpha ganglion cell: Na channel inactivation and removal of delayed-rectifier K channel (KDR) inactivation. Importantly, both mechanisms act within the physiological range of Vm, and both mechanisms show the appropriate time course to suppress visually-evoked firing during periods of high contrast. Below, we consider the evidence for these two mechanisms, their key properties for evoking adaptation, their interaction with each KU-55933 order Montelukast Sodium other and with synaptic inputs, and their presence in other retinal cell types and neural circuits. One intrinsic mechanism for contrast adaptation, Na channel inactivation, was identified

originally in studies of isolated salamander ganglion cells of unknown type (Kim and Rieke, 2001 and Kim and Rieke, 2003). In these cells, the Na current could be studied directly to characterize activation and inactivation properties. Slow recovery from inactivation (>200 msec) explained low-output gain at high contrast because of the reduced pool of available Na channels, and there was little or no apparent involvement of Ca or K channels (Kim and Rieke, 2001 and Kim and Rieke, 2003). Our results show a similar Na channel mechanism in the intact OFF Alpha ganglion cell. The maximum slope of the action potential, a proxy measure of Na current, suggested reduced channel availability after periods of depolarization and firing (Figure 5). Furthermore, the suppressed firing persisted in the presence of multiple blockers of K and Ca channels, consistent with a Na channel mechanism (Figure 6 and Figure 7). We also identified an intrinsic mechanism for adaptation mediated by KDR channels. In intact cells, brief hyperpolarization within the physiological range (∼10 mV negative to Vrest) reduced subsequent firing to a depolarizing test pulse or contrast stimulus (Figure 1, Figure 2 and Figure 3).