Transducer properties of a mechanoreceptor : an electrophysiological and pharmacological study of the crayfish stretch receptor
Author: Lin, Jiahui
Date: 2000-09-15
Location: Fysiologens förläsningssal, von Eulers väg 4
Time: 9.00
Department: Institutionen för fysiologi och farmakologi / Department of Physiology and Pharmacology
Abstract
The abdominal stretch receptor organ of the crayfish, an analog to the
human muscle spindle, contains one slowly adapting (SA) and one rapidly
adapting (RA) receptor neuron. The general aims of this project were to
elucidate, in the SA and RA neurons, the participation of voltagegated Na+
and K+ channels in overall transducer process and adaptation, and to
study possible blocking agents specific to mechanosensitive (MS)
channels. The two-electrode current and voltage clamp techniques were
used to record whole cell membrane potential and current; macropatch and
single channel recordings were made using the patch clamp technique after
the neuronal membrane was enzymatically freed from covering glial cells.
In the SA neuron at least two populations of Na+ channels may be present
in the soma, axon hillock and axon. In the RA neuron the majority of Na+
channels were found in axon about 250 gin away from the soma, and only
one population of Na+ channels seemed to be present. In SA neuron,
voltage gated Na+ and K+ channels were more concentrated in the part of
the soma close to the axon hillock, and their current densities were
decreased towards the dendrites. A low conductance (13 pS) outward
rectifying, voltage gated K+ channel was characterized in the SA neuron.
It was activated by depolarization of > 20 mV, and its single channel
current amplitude and open probability were voltage dependent. The
averaged current showed a pronounced delay in activation with little
inactivation within 80 ms. At least two closed states preceded two open
states. This 13 pS delayed rectifier is important in the repolarization
of the action potentials. These results suggest that the action potential
initiation site differs in SA and RA neurons and that the spatial
distribution is an important factor in the difference between their
excitable and adaptive properties.
The effects on the transducer properties of four local anesthetics
(lidocaine, its meta-isomer LL33, tetracaine and bupivacaine) and a
calmodulin antagonist, CGS 9343B were investigated in SA neurons.
Lidocaine reversibly increased the receptor current by a major K+
conductance increase through the MS channels, whereas LL33, bupivacaine
and tetracaine reversibly reduced the current in a dose-dependent way
without changing the passive membrane conductance. CGS 9343B reversibly
blocked the receptor current in a voltage- and dosedependent manner (Kd =
26.8 [my]M). The block was stimulus-independent, and extracellular Ca2+
had no effect on it. The local anesthetic effects, whether activating or
blocking MS channels, were correlated to the oil:water distribution
coefficients. CGS 9343B, in addition to accumulating in the lipid
membrane, may also interact with MS channel proteins.
In summary, these studies indicate that several kinds of voltage-gated Na+
and K+ channels are present in SA and RA neurons, and their differing
relative occurrence and spatial distribution suggest that these channels
play important roles in the generation of impulses and adaptation
behaviours in the SA and RA neurons. The four local anesthetics and the
calmodulin antagonist can either activate or block the NIS channels in
the dendrites of the receptor neuron probably by interference with the
lipid phase, yielding useful information about the properties of the MS
channels.
List of papers:
I. Lin JH, Rydqvist B (1999). "Different spatial distributions of sodium channels in the slowly and rapidly adapting stretch receptor neuron of the crayfish" Brain Res 830(2): 353-357
Pubmed
II. Lin JH, Sand P, Rydqvist B (1999). "Macrocurrents of voltage gated Na+ and K+ channels from the crayfish stretch receptor neuronal soma" Neuroreport 10(12): 2503-2507
Pubmed
III. Lin JH, Rydqvist B (2000). "Characterization of a delayed outward rectifier potassium channel in the slowly adapting stretch receptor neuron of crayfish" (Manuscript)
IV. Lin JH, Rydqvist B (1999). "The mechanotransduction of the crayfish stretch receptor neurone can be differentially activated or inactivated by local anaesthetics" Acta Physiol Scand 166(1): 65-74
Pubmed
V. Lin J, Rydqvist B (2000). "Inhibition of mechanotransducer currents in crayfish sensory neuron by CGS 9343B, a calmodulin antagonist" Eur J Pharmacol 397(1): 11-17
Pubmed
I. Lin JH, Rydqvist B (1999). "Different spatial distributions of sodium channels in the slowly and rapidly adapting stretch receptor neuron of the crayfish" Brain Res 830(2): 353-357
Pubmed
II. Lin JH, Sand P, Rydqvist B (1999). "Macrocurrents of voltage gated Na+ and K+ channels from the crayfish stretch receptor neuronal soma" Neuroreport 10(12): 2503-2507
Pubmed
III. Lin JH, Rydqvist B (2000). "Characterization of a delayed outward rectifier potassium channel in the slowly adapting stretch receptor neuron of crayfish" (Manuscript)
IV. Lin JH, Rydqvist B (1999). "The mechanotransduction of the crayfish stretch receptor neurone can be differentially activated or inactivated by local anaesthetics" Acta Physiol Scand 166(1): 65-74
Pubmed
V. Lin J, Rydqvist B (2000). "Inhibition of mechanotransducer currents in crayfish sensory neuron by CGS 9343B, a calmodulin antagonist" Eur J Pharmacol 397(1): 11-17
Pubmed
Issue date: 2000-08-25
Publication year: 2000
ISBN: 91-628-4210-2
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