Fine Tuning of Excitability by KCa Channels in Mudpuppy Parasympathetic Neurons

Abstract

Mudpuppy parasympathetic cardiac neurons generate spontaneous miniature outward currents (SMOCs) that result from the simultaneous activation of large conductance calcium activated (Kca) channels by Ca 2+ released from caffeineand ryanodine-sensitive intraceliular stores (Satin and Adams 1987; Merriam et ah, 1999; Scornik et al, 2001). The present article summarizes recent findings on SMOC regulation and on the role of these currents on action potential (AP) generation. The data presented in this article suggest that spatial distribution determines differential roles of Kca channels, in the generation and repolarization of AP in parasympathetic neurons from the mudpuppy cardiac ganglia. Parasympathetic cardiac neurons, like other autonomic neurons, express a number of different voltageand ligand-gated potassium channels in their plasma membranes that are important determinants of membrane potential and neuronal excitability (Brown 1988; Rudy 1988; Adams and Harper 1995). Among these different potassium conductances, Kca channels have been shown particularly, to play a key role in determining resting membrane potential, action potential repolarization and post action potential hyperpolarizations (Rudy 1988; Kaczorowski etal, 1996; Sah 1996). Activation of Kca channels is very dynamic because it is gated by elevation of the Ca concentration at the intraceliular side of the channel. Very localized elevations of Ca, which do not significantly elevate global intraceliular Ca, can activate Kca channels. Thus, physiological activation of Kca channels may be coupled to highly localized changes of ceil Ca. Although spontaneous miniature outward currents (SMOCs) were described in neurons over two decades ago, their physiological role remained unclear.