Journal article

Fast Ca2+-induced potentiation of heat-activated ionic currents requires cAMP/PKA signaling and functional AKAP anchoring


Authors listDistler, C; Rathee, PK; Lips, KS; Obreja, O; Neuhuber, W; Kress, M

Publication year2003

Pages2499-2505

JournalJournal of Neurophysiology

Volume number89

Issue number5

ISSN0022-3077

DOI Linkhttps://doi.org/10.1152/jn.00713.2002

PublisherAmerican Physiological Society


Abstract

Calcium influx and the resulting increase in intracellular calcium concentration ([Ca2+](i)) can induce enhanced sensitivity to temperature increases in nociceptive neurons. This sensitization accounts for heat hyperalgesia that is regularly observed following the activation of excitatory inward currents by pain-producing mediators. Here we show that rat sensory neurons express calcium-dependent adenylyl cyclases (AC) using RT-PCR and nonradioactive in situ hybridization. Ionomycin-induced rises in [Ca2+](i)-activated calcium-dependent AC and caused translocation of catalytic protein kinase A subunit. Elevation of [Ca2+](i) finally resulted in a significant potentiation of heat-activated currents and a drop in heat threshold. This was not prevented in the presence of suramin that nonspecifically uncouples G protein-dependent receptors. The sensitization was, however, inhibited when the specific PKA antagonist PKI14-22 was added to the pipette solution or when PKA coupling to A kinase anchoring protein ( AKAP) was disrupted with InCELLect StHt-31 uncoupling peptide. The results show that heat sensitization in nociceptive neurons can be induced by increases in [Ca2+](i) and requires PKA that is functionally coupled to the heat transducer, mostly likely vanilloid receptor VR-1. This calcium-dependent pathway can account for the sensitizing properties of many excitatory mediators that activate cationic membrane currents.




Citation Styles

Harvard Citation styleDistler, C., Rathee, P., Lips, K., Obreja, O., Neuhuber, W. and Kress, M. (2003) Fast Ca2+-induced potentiation of heat-activated ionic currents requires cAMP/PKA signaling and functional AKAP anchoring, Journal of Neurophysiology, 89(5), pp. 2499-2505. https://doi.org/10.1152/jn.00713.2002

APA Citation styleDistler, C., Rathee, P., Lips, K., Obreja, O., Neuhuber, W., & Kress, M. (2003). Fast Ca2+-induced potentiation of heat-activated ionic currents requires cAMP/PKA signaling and functional AKAP anchoring. Journal of Neurophysiology. 89(5), 2499-2505. https://doi.org/10.1152/jn.00713.2002


Last updated on 2025-24-06 at 15:31