Neuropeptides 5: 253-256, 1984 DYNORPRIN REDUCES VOLTAGE-DEPENDENT CALCIUM CONDUCTANCE OF MOUSE DORSAL ROOT GANGLION NEURONS

Dynorphin A (DYN)(l pM) decreased somatic calcium-dependent action potential (CAP) duration of a portion of dorsal root ganglion (DRG) neurons in a naloxone reversible manner. Responses to DYN differed from responses to Leu-enkephalin in that only DYN decreases of somatic CAP duration were associated with decreased action potential after hyperpolarization and persisted after intracellular injection of the potassium channel blocker cesium. While Leu-enkephalin at 10 pM did not affect somatic CAP duration of DRG neurons impaled with cesium-filled micropipettes, dynorphin A (l-8), dynorphin B, and 8-neoendorphin were effective at 1 uM. During single electrode voltage clamp, DYN decreased inward current in a portion of DRG neurona under conditions that predominately isolated calcium current. Leak current was unaffected by dynorphin A. Therefore, we suggest that DYN decreases voltage-dependent calcium conductance. The action on calcium conductance appears specific for opioids with affinity for kappa-receptors. INTRODUCTION In dorsal horn of the spinal cord, approximately 50% of opioid binding is thought to occur on primary afferents (1,2). Consistent with this observation, opioids have been reported to depress neurotransmitter release from primary afferent terminals (3,4,5). In addition to being localized on primary afferents, opioid receptors are present on the somata of dorsal root ganglion(DRG) neurons in vivo (6) and also grown in primary dissociated cell culture (5,7). -Binding of opioids to receptors on DRG neuron somata has been shown to result in a decrease of calcium-dependent action potential (CAP) duration (5,7). Interestingly, a similar effect of opioids on calcium entry at DRG neuron terminals would result in decreased neurotransmitter release and, thus, opioid receptors on DRG neuron somata and terminals are likely to be functionally similar. In this study we compare the actions of dynorphin A (DYN) and Leu-enkephalin (L-ENR) on DRG neuron somatic CAPS and calcium-dependent currents. METHODS Preparation of mouse spinal cord and DRG co-cultures and electrophysio-