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Exogenous ATP induces electrical membrane responses in fibroblasts
Experimental Cell Research
|June 1, 1984
Summary
Exogenous adenosine triphosphate (ATP) and adenosine diphosphate (ADP) trigger cell membrane hyperpolarization in fibroblasts by increasing potassium (K+) permeability. These responses are mediated by P2-purinoceptors and can lead to receptor desensitization.
Area of Science:
- Cellular physiology
- Molecular pharmacology
- Purinergic signaling
Background:
- Fibroblasts are crucial connective tissue cells involved in various physiological processes.
- Purinergic signaling, mediated by extracellular nucleotides like ATP, plays a significant role in cell communication and function.
- The specific mechanisms and receptors involved in fibroblast responses to purinergic agonists require further elucidation.
Purpose of the Study:
- To investigate the effects of exogenous adenosine triphosphate (ATP) on the membrane potential of mouse fibroblastic L cells.
- To characterize the nature of the cellular response to ATP, including receptor desensitization and the involvement of specific purinergic receptors.
- To determine if similar responses are observed in human fibroblasts.
Main Methods:
- Electrophysiological recordings were used to measure changes in membrane potential of cultured mouse fibroblastic L cells.
- Cells were treated with varying concentrations of exogenous ATP, adenosine diphosphate (ADP), and non-hydrolyzable ATP analogue (AMP-PNP).
- Intracellular injections of ATP and the effects of the antagonist antazoline were also examined.
Main Results:
- Exogenous ATP (≥ 0.2 mM) induced a transient hyperpolarization in L cells, attributed to increased membrane permeability to potassium (K+).
- Intracellular ATP injection had no significant effect, suggesting the involvement of extracellular receptors.
- Responses were observed with AMP-PNP and ADP, but not AMP or adenosine, indicating specificity for P2-purinoceptors. Antazoline partially suppressed the ATP response. Human fibroblasts exhibited similar ATP/ADP-induced responses.
Conclusions:
- Exogenous ATP and ADP activate P2-purinoceptors on mouse and human fibroblasts, leading to membrane hyperpolarization.
- The observed desensitization suggests a dynamic regulation of purinergic signaling pathways.
- These findings highlight the role of purinergic signaling in fibroblast physiology and potential therapeutic targets.