In:
Journal of Neurophysiology, American Physiological Society, Vol. 87, No. 6 ( 2002-06-01), p. 2844-2850
Abstract:
Among autonomic neurons, sympathetic neurons of the major pelvic ganglia (MPG) are unique by expressing low-voltage–activated T-type Ca 2+ channels. To date, the T-type Ca 2+ channels have been poorly characterized, although they are believed to be potentially important for functions of the MPG neurons. In the present study, thus we investigated characteristics and molecular identity of the T-type Ca 2+ channels using patch-clamp and RT-PCR techniques. When the external solution contained 10 mM Ca 2+ as a charge carrier, T-type Ca 2+ currents were first activated at −50 mV and peaked around −20 mV. Besides the low-voltage activation, T-type Ca 2+ currents displayed typical characteristics including transient activation/inactivation and voltage-dependent slow deactivation. Overlap of the activation and inactivation curves generated a prominent window current around resting membrane potentials. Replacement of the external Ca 2+ with 10 mM Ba 2+ did not affect the amplitudes of T-type Ca 2+ currents. Mibefradil, a known T-type Ca 2+ channel antagonist, depressed T-type Ca 2+ currents in a concentration-dependent manner (IC 50 = 3 μM). Application of Ni 2+ also produced a concentration-dependent blockade of T-type Ca 2+ currents with an IC 50 of 10 μM. The high sensitivity to Ni 2+ implicates α1H in generating the T-type Ca 2+ currents in MPG neurons. RT-PCR experiments showed that MPG neurons predominantly express mRNAs encoding splicing variants of α1H (called pelvic Ta and Tb, short and long forms of α1H, respectively). Finally, we tested whether the low-threshold spikes could be generated in sympathetic MPG neurons expressing T-type Ca 2+ channels. When hyperpolarizing currents were injected under a current-clamp mode, sympathetic neurons produced postanodal rebound spikes, while parasympathetic neurons were silent. The number of the rebound spikes was reduced by 10 μM Ni 2+ that blocked 50% of T-type Ca 2+ currents and had a little effect on HVA Ca 2+ currents in sympathetic MPG neurons. Furthermore, generation of the rebound spikes was completely prevented by 100 μM Ni 2+ that blocked most of the T-type Ca 2+ currents. In conclusions, T-type Ca 2+ currents in MPG neurons mainly arise from α1H among the three isoforms (α1G, α1H, and α1I) and may contribute to generation of low-threshold spikes in sympathetic MPG neurons.
Type of Medium:
Online Resource
ISSN:
0022-3077
,
1522-1598
DOI:
10.1152/jn.2002.87.6.2844
RVK:
XA 10000 ; XA 552555
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
80161-6
detail.hit.zdb_id:
1467889-5
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