These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: High-voltage-activated calcium currents in basal forebrain neurons during aging.
    Author: Murchison D, Griffith WH.
    Journal: J Neurophysiol; 1996 Jul; 76(1):158-74. PubMed ID: 8836216.
    Abstract:
    1. Both conventional whole cell and perforated-patch voltage-clamp recordings were made of high-voltage-activated (HVA) calcium (Ca2+) channel currents in acutely dissociated medical septum and nucleus of the diagonal band neurons from young (1-3.5 mo) and aged (19-26.5 mo) Fischer 344 rats. Barium (Ba2+) was used as the charge carrier to minimize secondary Ca(2+)-induced conductances and Ca(2+)-induced inactivation. 2. When HVA currents generated by voltage ramps from a holding potential (Vh) of-60 mV were recorded within minutes after whole cell formation, no change in peak current density was observed between young (-44.7 +/- 2.5 pA/pF, mean +/- SE, n = 93) and aged (-44.2 +/- 2.1 pA/pF, n = 86) cells. However, currents recorded later with voltage step protocols revealed a reduction in peak current amplitudes and a trend toward larger peak current densities in aged cells. From a Vh of -60 mV and with steps to -10 mV, current densities were -21.5 +/- 1.9 pA/pF in young cells (n = 55) and -25.0 +/- 2.0 pA/pF in aged cells (n = 44). The differences in current densities recorded by the two protocols were explained by nonspecific current rundown and the development of a slow (min) inactivation process. Slow inactivation was different from conventional rundown of HVA currents because it was reversible with the use of perforated-patch recordings. 3. Perforated-patch recordings were used to characterize slow inactivation. There was significantly less slow inactivation in aged cells. When voltage steps (200 ms in duration, from -80 to -10 mV) were delivered at 12-s intervals, slow inactivation reduced the current after 15 min to 63 +/- 7% of control in young cells and 86 +/- 4% in aged cells (P = 0.028). When voltage steps were delivered at 20-s intervals, the current at the 15th step decreased to 93.4 +/- 1.5% of control in aged cells, compared with 86.6 +/- 1.6% in young (P = 0.007). There was less slow inactivation with increased intervals between voltage steps and with shorter step durations. There was also less inactivation with reduced concentration of charge carrier, indicating a current-dependent component to slow inactivation. Additionally, a voltage-dependent component was evident, because slow inactivation was increased at depolarized VhS. 4. Perforated-patch recordings were used to study at least four pharmacologically distinct fractions of HVA currents in both young and aged cells. Nifedipine (10 microM) blocked 16.9 +/- 2.8% and 23.6 +/- 2.5% of the HVA currents in young and aged cells, respectively. omega-Conotoxin GVIA (500 nM) blocked 53.2 +/- 5.8% in young and 53.6 +/- 2.9% in aged cells. In young cells, omega-agatoxin IVA (200-400 nM) blocked 28.4 +/- 2.2% of the HVA current, and it blocked 29.9 +/- 2.8% in aged cells. A fraction of the current (young cells: 13.8 +/- 2.2%; aged cells: 11.4 +/- 1.6%) was resistant to a combination of all three antagonists. Cadmium (100 microM) completely blocked the remaining HVA current. No significant age-related differences in the HVA current fractions were observed. 5. The HVA current density, current-voltage relationship, and voltage-dependent activation were unchanged with age. However, slow inactivation of HVA currents was reduced in aged cells. The age-related difference in HVA Ca2+ currents reported here suggests a possible mechanism by which Ca2+ homeostasis may be altered in aged neurons.
    [Abstract] [Full Text] [Related] [New Search]