Multiple modulatory effects of dopamine on calcium channel kinetics in adult rat sensory neurons.
1. The aim of this research was to study the modulatory effects induced on high-voltage-activated (HVA) calcium channels and pharmacologically isolated subtypes through dopamine receptor activation. 2. The experiments were carried out on acutely isolated adult rat sensory neurons, recorded by means of the whole-cell patch-clamp technique. 3. At saturating concentrations dopamine was effective in inducing: (a) a voltage-dependent prolongation of activation kinetics, (b) a voltage-independent scaling down of the currents without any changes in activation and inactivation kinetics, and (c) an acceleration of inactivation kinetics, not affected by a positive conditioning prepulse. 4. These three inhibitory effects were observed on N- and P/Q-type currents, whereas only a voltage-independent scaling up and/or scaling down was observed on L-type current. 5. The inhibitory effects were sometimes observed in isolation in different neurons, but more frequently they were variously combined in the same cell. A correlation analysis of these effects shows no relationship between them, corroborating the conclusion that they are mechanistically distinct. 6. The existence of an inactivating effect accounts for the occurrence of a voltage-dependent inhibitory effect in some cells without an apparent slowing down of activation kinetics, since the increased inactivation may mask the slow component of the activation. 7. The multiple modulatory effects on calcium channels, even on pharmacologically separated N-, L- and P/Q-currents, suggest that pharmacological and functional classifications do not necessarily match completely. 8. The multiple modulatory effects on HVA calcium currents may play a prominent role both in controlling the integrative properties of neurons and in regulating output at a presynaptic level.
Formenti
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Institute of Human Physiology II, University of Milan, 32 Via Mangiagalli, I-20133 Milan, Italy. aforment@imiucca.csi.unimi.it
Martina
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Plebani
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Mancia
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D000818:Animals; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D004298:Dopamine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D001464:Barium; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D004298:Dopamine