Functional coupling between ryanodine receptors and L-type calcium channels in neurons

IN skeletal muscle, L-type Ca2+ channels act as voltage sensors to control ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum(1). It has recently been demonstrated that these ryanodine receptors generate a retrograde signal that modifies L-type Ca2+-channel activity(2). Here we demonstrate a tight functional coupling between ryanodine receptors and L-type Ca2+ channel in neurons, In cerebellar granule cells, activation of the type-1 metabotropic glutamate receptor (mGluR1) induced a large, oscillating increase of the L-type Ba2+ current. Activation occurred independently of inositol 1,4,5-trisphosphate and classical protein kinases, but was mimicked by caffeine and blocked by ryanodine, The kinetics of this blockade were dependent on the frequency of Ba2+ current stimulation, Both mGluR1- and caffeine-induced increase in L-type Ca2+-channel activity persisted in inside-out membrane patches, In these excised patches, ryanodine suppressed both the mGluR1- and caffeine-activated L-type Ca2+ channels. These results demonstrate a novel mechanism for Ca2+-channel modulation in neurons.