RAPID COMMUNICATION Inhibition of Dendritic Calcium Influx by Activation of G-Protein–Coupled Receptors in the Hippocampus

Chen, Huanmian and Nevin A. Lambert. Inhibition of dendritic located on cell bodies, whereas R-type and low-threshold calcium influx by activation of G-protein–coupled receptors in the T-type channels are relatively abundant on dendrites (Chrishippocampus. J. Neurophysiol. 78: 3484–3488, 1997. Gi proteins tie et al. 1995; Magee and Johnston 1995). Pertussis toxininhibit voltage-gated calcium channels and activate inwardly rectisensitive G-proteins (Gi /Go) usually inhibit high-threshold fying K channels in hippocampal pyramidal neurons. The effect channels of the Nand P/Q-types, whereas Land R-types of activation of G-protein–coupled receptors on action potentialare less sensitive or insensitive (Hille 1994), and low-threshevoked calcium influx was examined in pyramidal neuron dendrites old, T-type channels are usually not inhibited (Guyon and with optical and extracellular voltage recording. We tested the Leresche 1995). Thus the calcium channels present on pyrahypotheses that 1) activation of these receptors would inhibit calmidal neuron dendrites may be less susceptible to direct cium channels in dendrites; 2) hyperpolarization resulting from K channel activation would deinactivate low-threshold, T-type inhibition by G-proteins than those on cell bodies or termicalcium channels on dendrites, increasing calcium influx mediated nals. In addition, recent evidence suggests that direct inhibiby these channels; and 3) activation of these receptors would intion of calcium channels by G-proteins requires intact synhibit propagation of action potentials into dendrites, and thus inditaxin, a protein that is targeted to axon terminals (Stanley rectly decrease calcium influx. Activation of adenosine receptors, and Mirotznik 1997). Second, Gi proteins also activate inwhich couple to Gi proteins, inhibited calcium influx in cell bodies wardly rectifying K channels in pyramidal cells (reviewed and proximal dendrites without inhibiting action-potential propagain Jan and Jan 1997; Hille 1994), hyperpolarizing dendrites. tion into the proximal dendrites. Inhibition of dendritic calcium In intact dendrites this could deinactivate T-type channels influx was not changed in the presence of 50 mM nickel, which and increase calcium influx mediated by these channels. On preferentially blocks T-type channels, suggesting influx through the other hand, hyperpolarization could inhibit active propathese channels is not increased by activation of G-proteins. Adenosine inhibited propagation of action potentials into the distal gation of action potentials into dendrites (Richardson et al. branches of pyramidal neuron dendrites, leading to a threeto 1987; Turner et al. 1989) and indirectly decrease calcium fourfold greater inhibition of calcium influx in the distal dendrites influx. than in the soma or proximal dendrites. These results suggest that The coincident activation of K channels and inhibition voltage-gated calcium channels are inhibited in pyramidal neuron of some (but not all) Ca channels makes the net effect of dendrites, as they are in cell bodies and terminals and that G-protein–coupled receptor activation on action-potential– G-protein–mediated inhibition of action-potential propagation can evoked calcium influx in dendrites difficult to predict. We contribute substantially to inhibition of dendritic calcium influx. have performed a series of experiments to measure inhibition