Prolactin regulates tuberoinfundibular dopamine neuron discharge pattern: novel feedback control mechanisms in the lactotrophic axis.
Balance in the body's hormonal axes depends on feedback onto neuroendocrine hypothalamic neurons. This phenomenon involves transcriptional and biosynthetic effects, yet less is known about the potential rapid modulation of electrical properties. Here, we investigated this issue in the lactotrophic axis, in which the pituitary hormone prolactin is tonically inhibited by tuberoinfundibular dopamine (TIDA) neurons located in the hypothalamic arcuate nucleus. Whole-cell recordings were performed on slices of the rat hypothalamus. In the presence of prolactin, spontaneously oscillating TIDA cells depolarized, switched from phasic to tonic discharge, and exhibited broadened action potentials. The underlying prolactin-induced current is composed of separate low- and high-voltage components that include the activation of a transient receptor potential-like current and the inhibition of a Ca(2+)-dependent BK-type K(+) current, respectively, as revealed by ion substitution experiments and pharmacological manipulation. The two components of the prolactin-induced current appear to be mediated through distinct signaling pathways as the high-voltage component is abolished by the phosphoinositide 3-kinase blocker wortmannin, whereas the low-voltage component is not. This first description of the central electrophysiological actions of prolactin suggests a novel feedback mechanism. By simultaneously enhancing the discharge and spike duration of TIDA cells, increased serum prolactin can promote dopamine release to limit its own secretion with implications for the control of lactation, sexual libido, fertility, and body weight.
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. David.Lyons@ki.se
David J
DJ
Lyons
Arash
A
Hellysaz
Christian
C
Broberger
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology*; D055724:Electrophysiological Phenomena; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007202:Indicators and Reagents; D007473:Ion Channels / Q000502:physiology; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001896:Boron Compounds; D002118:Calcium; D004298:Dopamine; D007202:Indicators and Reagents; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011388:Prolactin; C538758:2-aminoethyl diphenylborinate