FUNCTIONAL COUPLING BETWEEN RYANODINE RECEPTORS AND L-TYPE CALCIUM CHANNELS IN NEURONS

IN skeletal muscle, L-type Ca2+ channels act as voltage sensors to con trol ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum(1 ). It has recently been demonstrated that these ryanodine receptors ge nerate 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 ce lls, activation of the type-1 metabotropic glutamate receptor (mGluR1) induced a large, oscillating increase of the L-type Ba2+ current. Act ivation occurred independently of inositol 1,4,5-trisphosphate and cla ssical protein kinases, but was mimicked by caffeine and blocked by ry anodine, The kinetics of this blockade were dependent on the frequency of Ba2+ current stimulation, Both mGluR1- and caffeine-induced increa se in L-type Ca2+-channel activity persisted in inside-out membrane pa tches, In these excised patches, ryanodine suppressed both the mGluR1- and caffeine-activated L-type Ca2+ channels. These results demonstrat e a novel mechanism for Ca2+-channel modulation in neurons.