Acta Physiologica 2009; Volume 197, Supplement 672
The 60th National Congress of the Italian Physiological Society
CYCLIC AMP INHIBITS INWARDLY RECTIFYING POTASSIUM CURRENTS CAUSING DEPOLARIZATION OF MEDIUM SPINY NEURONS IN THE NUCLEUS ACCUMBENS THROUGH A PKA-INDEPENDENT PATHWAY.
Abstract number: P134
PODDA1 MV, RICCARDI1 E, D'ASCENZO1 M, AZZENA1 GB, GRASSI1 C
1Institute of Human Physiology, Catholic University, Rome; (Italy)email@example.com
Aim of the study was to investigate whether and how cAMP affects the resting membrane potential of medium spiny neurons (MSNs) in the nucleus accumbens (NAc).
Application of the adenylyl cyclase stimulator forskolin (FSK, 20 mM) to NAc slices elicited membrane depolarizations of 4.1±0.7 mV. In voltage-clamp FSK induced inward currents of -17.8±1.7 pA.
Similar results were obtained by applying the cAMP analogue 0.5 mM dB-cAMP or intracellularly applying 1 mM cAMP. FSK and dB-cAMP-induced effects were unaffected by PKA, PKC or PLC activity suggesting a direct action of cAMP on ion channels. Furthermore FSK- and dB-cAMP-effects were associated to increased membrane input resistance, suggesting that inhibition of ion conductances underlies the cAMP's effects. Voltage-clamp experiments showed that FSK effects are due to inhibition of inward-rectifier K+ channels (Kir) because: i) they were never observed when Cs+ was present in the pipette solution; ii) they were abolished by BaCl2; iii) Kir currents elicited by hyperpolarizing voltage protocols were decreased by FSK; iv) net current inhibited by FSK showed inward rectification at hyperpolarized potentials and reversal potential of -89.3±1.2 mV, which shifted concurrently with extracellular K+ concentrations. Inhibition of Kir currents was also elicited by neurotransmitters coupled to cAMP signaling such as dopamine and noradrenaline.
cAMP excitatory effects may facilitate MSN transition from quiescent downstate to upstate.
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Acta Physiologica 2009; Volume 197, Supplement 672 :P134