Aspects of neuronal potassium channel function in rat genetic hypertension
Experience the future of the Tulane University Digital Library.
We invite you to visit the new Digital Collections website.
Description
The properties of voltage- and calcium-gated K+ channels were examined in sympathetic ganglion neurons acutely isolated from Spontaneously Hypertensive Rats (SHR) for alterations consistent with the elevated neuronal excitability associated with the exaggerated sympathetic outflow observed in this model of human essential hypertension Whole-cell voltage clamp recordings revue two contradictory alterations of the A-type K+ (IA) current of SHR neurons. The voltage-dependence of steady state (1.0 s) inactivation was shifted approximately 6 mV to more hyperpolarized potentials. Considered alone, the inactivations shift is consistent with increased neuronal excitability since the availability of IA to inhibit excitability would be decreased. However, the inactivation shift was offset by an increase in current density which was sufficient to normalize the amplitude of IA when compared physiological potentials. The time course of the onset of fast inactivation and recovery from inactivation were not altered, suggesting that the inactivation shift results from changes in the slow, or C-type inactivation mechanism. Preventing the development of hypertension in the SHR by long term angiotensin converting enzyme inhibition initiated at a prehypertensive age did not affect I A inactivation gating, suggesting that the inactivation shift is a primary alteration neuron properties in the SHR. Current density, on the other hand, was normal in adult SHR in which the development of hypertension as prevented, suggesting IA density elevates in the SHR secondarily to elevated arterial pressure Examination of neuronal firing properties under whole-cell current clamp demonstrated that changing the concentration of intracellular Ca2+ by whole-cell dialysis modulates sympathetic neuron excitability. Superior cervical ganglion sympathetic neurons from normotensive rats displayed hyperexcitability after dialysis with a Ca2+-free internal solution, manifested as repetitive spiking during 400 ms injections of depolarizing current. Dialysis with an internal solution containing [Ca2+] i ≈ 100 nM supported the expected phasic firing properties of these normotensive rat paravertebral neurons. However, the hyperexcitability of SHR sympathetic neurons was unexpectedly blunted following dialysis with the Ca2+-containing internal soluton. The nystatin perforated-patch technique was therefore employed to examine cell electrical behavior while preserving the cellular Ca2+ handling mechanisms. In the absence of whole-cell dialysis, a greater percentage of SHR neurons fired repetitively in response to long injections of depolarizing current, compared to neurons front normotensive rats. These data may indicate that the underling cellular mechanism that imparts hyperexcitability to SHR neurons may involve the handling of intracellular Ca2+ ions Given the key roll of large conductance Ca2+-activated K+ (maxi K) channels in the regulation of Ca2+ influx into sympathetic neurons these channels were examined as potential candidates underlying the altered neuronal function in the SHR. Properties of single, native maxi K channels in membrane patches excised from SHR and normotensive rat neurons were found to be similar, suggesting that maxi K channels may not contribute to the hyperexcitability of SHR neurons