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


Calcium-activated potassium (KCa) channels contribute to multiple neuronal properties including spike frequency and afterhyperpolarizing potentials (AHPs). KCa channels are classified as KCa1.1, KCa2, or KCa3.1 based on single-channel conductance and pharmacology. Ca2+-dependent AHPs in vertebrates are categorized as fast, medium, or slow. Fast and medium AHPs are generated by KCa1.1 and KCa2 channels, respectively. The KCa subtype responsible for slow AHPs is unclear. Prolonged, Ca2+-dependent AHPs have been described in several leech neurons. Unfortunately, apamin and other KCa blockers often prove ineffective in the leech. An alternative approach is to utilize KCa modulators, which alter channel sensitivity to Ca2+. Vertebrate KCa2 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 KCa2 channels underlie prolonged AHPs in these neurons and suggest that KCa2 modulators may serve as effective tools to explore the role of KCa channels in leech physiology.

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Fig. 7



Afterhyperpolarization or afterhyperpolarizing potential


1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid




Dorsal excitatory motor neuron 3


Hyperpolarization-activated and cyclic nucleotide-gated channels

Ih :

Hyperpolarization-activated current

KCa :

Calcium-activated potassium

N cell:

Nociceptive mechanosensory neuron



P cell:

Pressure-sensitive mechanosensory neuron


Postinhibitory rebound


Small conductance subtype of calcium-activated potassium channels

T cell:

Touch-sensitive mechanosensory neuron

V m :

Membrane potential


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The authors wish to thank David Weisblat, Tom Giarla, and Rachel Sterne-Marr for their insightful comments. All experiments are in accordance with current laws on animal experimentation and care in the USA.


This work was made possible by generous support from Siena College, including a CURCA summer research fellowship to Matthew I. Rebel.

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All authors contributed to data collection and analysis. The first draft of the manuscript was written by JDA and all authors commented on previous versions of the manuscript.

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Correspondence to James D. Angstadt.

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Angstadt, J.D., Rebel, M.I. & Connolly, M.K. Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech. J Comp Physiol A 207, 69–85 (2021). https://doi.org/10.1007/s00359-021-01462-w

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  • Afterhyperpolarizing potentials
  • Calcium-activated potassium
  • CyPPA
  • Leech
  • NS8593