Serotonin 5-HT(3) receptors on mechanosensitive neurons with cardiac afferents.
In rats, the mechanosensitive cardiorenal baroreflex influencing renal excretory function might be impaired by serotonin occurring in coronary arteries, e.g., in hypertension. Because the afferent limb of this reflex could be affected, we investigated the responses of nodose ganglion cells (one neuron of reflex) to osmotic, mechanical stress in presence or absence of the serotonin 5-HT(3) receptor agonist phenylbiguanide (PBG). Current-voltage relationships (from -100 to +50 mV) were obtained using cell patch recordings while the cells were exposed to control or hypoosmotic solutions to induce mechanical stress. This protocol was repeated after low doses of PBG (10 microM), angiotensin II (10 nM), or the stretch-activated channel blocker gadolinium (20 microM) were added to the extracellular medium (EM). Hypoosmotic EM induced significant changes in cellular conductance. The full-range current-voltage relationship allowed for the calculation of a mean reversal potential of -13 +/- 1.2 mV with respect to this change in cellular conductance (n = 44). This increase in conductance was impaired after addition of either PBG or gadolinium to the EM,which was statistically evaluated at a voltage of -80 mV, where influences of voltage-gated channels are not likely to interfere with the responses recorded. The serotonin 5-HT(3) receptor antagonist tropisetron (10 nM) prevented the PBG effect on conductance responses. Angiotensin II had no influence. Hence, serotonin might decrease the mechanical sensitivity of afferent cardiac nerves controlling renal sympathetic nerve activity.
Linz
Peter
P
Department of Internal Medicine, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Veelken
Roland
R
D000344:Afferent Pathways / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002478:Cells, Cultured; D004553:Electric Conductivity; D005682:Gadolinium / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D007038:Hypotonic Solutions; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013314:Stress, Mechanical; D000077526:Tropisetron
D001645:Biguanides; D007038:Hypotonic Solutions; D007211:Indoles; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000804:Angiotensin II; D000077526:Tropisetron; D005682:Gadolinium; C008846:phenyl biguanide