Different types of potassium channels underlie the long afterhyperpolarization in guinea-pig sympathetic and enteric neurons

Ca2+-activated K+ channels play an important role in the control of neuronal excitability via the generation of the afterhyperpolarization. While both small and large conductance Ca2+-activated K+ channels underlie afterhyperpolarizations in different neuron types, the role of intermediate conductance Ca2+-activated K+ channels (IKCa) in the generation of afterhyperpolarizations remains unclear. The effects of blockade of IKCa on guinea pig coeliac and ileal myenteric neurons were studied using single microelectrode current and voltage clamp. In coeliac neurons, TRAM-39, a selective blocker of IKCa, depressed the amplitude of the prolonged conductance underlying the slow afterhyperpolarization, (gKCa2) by 57%. In contrast, the conductance underlying the prolonged afterhyperpolarization in AH-type myenteric neurons was unaffected by TRAM-39, although it has been suggested that this AHP is mediated by IKCa. In both types of neurons, TRAM-39 did not alter the resting cell properties or the properties of the action potential. TRAM-39 had no effect on the amplitude of the fast component of the afterhyperpolarization present in sympathetic LAH neurons. The results of this study suggest that in sympathetic LAH neurons, activation of IKCa underlies at least part of the prolonged afterhyperpolarization while the nature of the channel underlying the AHP in enteric neurons remains unclear.