Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech.

Calcium-activated potassium (K) channels contribute to multiple neuronal properties including spike frequency and afterhyperpolarizing potentials (AHPs). K channels are classified as K1.1, K2, or K3.1 based on single-channel conductance and pharmacology. Ca-dependent AHPs in vertebrates are categorized as fast, medium, or slow. Fast and medium AHPs are generated by K1.1 and K2 channels, respectively. The K subtype responsible for slow AHPs is unclear. Prolonged, Ca-dependent AHPs have been described in several leech neurons. Unfortunately, apamin and other K blockers often prove ineffective in the leech. An alternative approach is to utilize K modulators, which alter channel sensitivity to Ca. Vertebrate K2 channels are targeted selectively by the positive modulator CyPPA and the negative modulator NS8593. Here we show that AHPs in identified motor and mechanosensory leech neurons are enhanced by CyPPA and suppressed by NS8593. Our results indicate that K2 channels underlie prolonged AHPs in these neurons and suggest that K2 modulators may serve as effective tools to explore the role of K channels in leech physiology.