Localized IP3-evoked Ca2+ release activates a K+ current in primary vagal sensory neurons

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 (I-IP3). Photorelease of caged IP3 evoked an I-IP3 that 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. I-IP3 was 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 I-IP3. These results indicated that I-IP3 was a Ca2+-dependent K+ current. I-IP3 was 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 muM) 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 I-IP3 requires 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.