Localized IP3-Evoked Ca2+Release Activates a K+Current in Primary Vagal Sensory Neurons

Abstract

Electrophysiological and microfluorimetric techniques were used to determine whether intracellular photorelease of caged IP3, and the consequent release of Ca2+, could trigger a Ca2+-activated K+current ( IIP3). Photorelease of caged IP3evoked an IIP3that averaged 2.36 ± 0.35 (SE) pA/pF in 24 of 28 rabbit primary vagal sensory neurons (nodose ganglion neurons, NGNs) voltage-clamped at –50 mV. IIP3was abolished by intracellular BAPTA (2 mM), a Ca2+chelator. Changing the K+equilibrium potential by increasing extracellular K+ion concentration caused a predicted Nernstian shift in the reversal potential of IIP3. These results indicated that IIP3was a Ca2+-dependent K+current. IIP3was unaffected by three common antagonists of Ca2+-activated K+currents: bath-applied iberiotoxin (50 nM) or apamin (100 nM), and intracellular 8-Br-cAMP (100 μM) included in the patch pipette. We have previously demonstrated that both IP3-evoked Ca2+release and Ca2+-induced Ca2+release (CICR) are co-expressed in NGNs and that CICR can trigger a Ca2+-activated K+current. In the present study, using caffeine, a CICR agonist, to selectively attenuate intracellular Ca2+stores, we showed that IP3-evoked Ca2+release occurs independently of CICR, but interestingly, that a component of IIP3requires CICR. These data suggest that IP3-evoked Ca2+release activates a K+current that is pharmacologically distinct from other Ca2+-activated K+currents in NGNs. We describe several models that explain our results based on Ca2+signaling microdomains in NGNs.