Inhibition of conditioned stimulus pathway phosphoprotein 24 expression blocks the reduction in A-type transient K⁺ current produced by one-trial in vitro conditioning of Hermissenda

Long-term intrinsic enhanced excitability is a characteristic of cellular plasticity and learning-dependent modifications in the activity of neural networks. The regulation of voltage-dependent K⁺ channels by phosphorylation/dephosphorylation and their localization is proposed to be important in the control of cellular plasticity. One-trial conditioning in Hermissenda results in enhanced excitability in sensory neurons, type B photoreceptors, of the conditioned stimulus pathway. Conditioning also regulates the phosphorylation of conditioned stimulus pathway phosphoprotein 24 (Csp24), a cytoskeletal-related protein containing multiple β-thymosin-like domains. Recently, it was shown that the downregulation of Csp24 expression mediated by an antisense oligonucleotide blocked the development of enhanced excitability in identified type B photoreceptors after one-trial conditioning without affecting short-term excitability. Here, we show using whole-cell patch recordings that one-trial in vitro conditioning applied to isolated photoreceptors produces a significant reduction in the amplitude of the A-type transient K⁺ current (I_A) detected 1.5-16 h after conditioning. One-trial conditioning produced a depolarized shift in the steady-state activation curve of I_A without altering the inactivation curve. The conditioning-dependent reduction in I_A was blocked by preincubation of the photoreceptors with Csp antisense oligonucleotide. These results provide an important link between Csp24, a cytoskeletal protein, and regulation of voltage-gated ion channels associated with intrinsic enhanced excitability underlying pavlovian conditioning.