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Recovery from the rapid desensitization of nicotinic acetylcholine receptor channels on mouse muscle
Abstract:
Pulses of acetylcholine (ACh) applied to outside-out patches of embryonic-like muscle membrane elicited channel currents which declined rapidly (tau d = 10-60 ms) due to desensitization. Recovery from desensitization was determined by pulse pairs, varying the pulse interval. When the pulse interval was about 300 ms, the response to the second pulse was about half that to the first pulse, i.e. about half of the channels had recovered from desensitization. The results are discussed in the frame of a cyclic reaction scheme. If this scheme includes high affinity binding of ACh to desensitized receptors, it can also explain the finding that low ACh concentrations (less than or equal to 1 microM) largely desensitize the receptors, but elicit very little channel opening.
Insights
Acetylcholine (ACh) causes rapid muscle channel desensitization. Recovery from this desensitization occurs over hundreds of milliseconds, suggesting a cyclic reaction scheme involving high-affinity binding.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- Acetylcholine (ACh) is a key neurotransmitter in muscle function.
- Muscle membrane channels exhibit rapid desensitization upon ACh exposure.
- Understanding desensitization kinetics is crucial for muscle physiology.
Purpose of the Study:
- To quantify the desensitization and recovery rates of embryonic-like muscle membrane channels.
- To elucidate the mechanism underlying ACh-induced channel desensitization.
- To investigate the role of high-affinity binding in receptor response.
Main Methods:
- Utilized outside-out patches of embryonic-like muscle membrane.
- Applied pulses of acetylcholine (ACh) to elicit channel currents.
- Employed paired-pulse stimulation with varying intervals to assess recovery from desensitization.
Main Results:
- ACh pulses induced rapidly declining channel currents (tau d = 10-60 ms) due to desensitization.
- Recovery from desensitization was approximately 50% complete after a 300 ms interval.
- Low ACh concentrations (<1 microM) caused significant desensitization with minimal channel opening.
Conclusions:
- The desensitization and recovery kinetics are consistent with a cyclic reaction scheme.
- High-affinity binding of ACh to desensitized receptors explains low-concentration paradox.
- This mechanism is critical for regulating muscle excitability and response.