The superior cervical ganglion (SCG) is the largest of the sympathetic chain
ganglia which control a number of autonomic cardiovascular reflexes via neural activity
in the postganglionic nerve trunk. In addition to the large principal neurons, these
ganglia contain a minority population of smaller cells, the small intensely fluorescent or
SIF cells, so named because of their intense fluorescence following treatments which
reveal the presence of endogenous catecholamines (mainly dopamine in the rat). The
physiological functions of the SIF cells are largely unknown and various roles have been
proposed including (i) dopaminergic interneuron, which modulates ganglionic
transmission, (ii) endocrine function, since many of them have a close association with
the vasculature and (iii) chemosensory function, similar to that of the arterial
chemoreceptors which sense blood gases and pH. Understanding the physiological role
of SIF cells has been hampered by their small size, sparse distribution and relative
inaccessibility, all of which render microelectrode electrophysiological studies difficult.
In this thesis these limitations were overcome by use of (i) dissociated cell cultures of the
rat SCG, in which growth conditions favoured SIF cell survival but not that of the
principal neurons, and (ii) the novel high resolution patch clamp/whole cell recording
technique which is ideal for the study of the electrophysiology of small cells.
The ionic currents, which underlie many basic electrophysiological processes,
were characterized in 5-16 day old cultures of SIF cells obtained from the SCG of
neonatal rats. The main methodology consisted of whole cell recording under voltage
clamp conditions, which permit the study of membrane ionic currents. Five main ionic
currents were identified in all of the SIF cells ( > 100) studied: (i) a fast transient inward
Na+ current, sensitive to the well-known blocker of voltage-gated Na+ channels i.e.
tetrodotoxin or TTX; (ii) the delayed rectifier outward K+ current that is found in a
variety of cell types; (iii) a Ca2+- activated outward K+ current, sensitive to Ca2+ channel
blockers; (iv) a transient inward Ca2+ current which appears to be carried by N-type
Ca2+ channels and (v) a slower, sustained inward Ca2+ current which appears to be
carried by L-type Ca2+ channels. In addition a third type of outward K+ current, the fast
transient K+ current or lA, was found in SIF cells obtained from 3-7 day old rats, but not
from 1 day old rats. It therefore appears that this lA current, which is known to
modulate firing frequency in neurons develops rapidly in vivo during the first postnatal
week. This broad repertoire of ion channels in SIF cells suggests several possible sites
for modulation by various agents including neurotransmitters, neuromodulators, or other
chemosensitive agents. Since SIF cells were recently proposed to have arterial
chemoreceptor function similar to glomus cells, the effect of one such stimulus, i.e. an
acidic (intracellular) pH, was tested. It has recently been suggested that a decrease in
intracellular pH is part of the pathway responding to extracellular stimuli in the glomus
cell (Stea, Alexander and Nurse, in press). Acidification of the SIF cell's cytoplasm with
the K+/H+ ionophore nigericin resulted in a suppression of both the fast inward Na+
current as well as the outward K+ current. However, these effects do not appear to beunique to SIF cells and therefore the possibility of a chemoreceptor role m the
cardiovascular system requires further study.
In summary, the characterization of the various ionic currents in SIF cells
resulting from this thesis provides the necessary background which should eventually
resolve not only the question of the physiological role of SIF cells in autonomic ganglia,
but also help to understand the underlying mechanisms responsible for SIF cell function. / Thesis / Master of Science (MS)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22637 |
| Date | January 1999 |
| Creators | Alexander, Stephen A. |
| Contributors | Nurse, C.A, Biology |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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