title: Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.
abstract: Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.
authors.affiliation: University of Texas Health Science Center at San Antonio, 78229-3900, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Belugin
authors.forename: Steve
authors.initials: S
authors.lastname: Mifflin
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D006977:Hypertension, Renal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000502:physiology*; D011726:Pyridinium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017552:Solitary Nucleus / Q000473:pathology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015221:Potassium Channels; D011726:Pyridinium Compounds; D026941:Sodium Channel Blockers; C076868:4-(4-dihexadecylaminostyryl)-N-methylpyridium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine