Common ionic mechanisms of excitation by substance P and other transmitters in guinea‐pig submucosal neurones.

K. Z. Shen, A. Surprenant

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

1. Intracellular recordings were made from submucosal neurones and single‐electrode voltage‐clamp methods were used to record membrane currents. The actions of substance P (SP), 5‐hydroxytryptamine (5‐HT), muscarine, vasoactive intestinal polypeptide (VIP), forskolin and nerve stimulation were studied. 2. Substance P, 5‐HT (in the presence of 5‐HT3 receptor antagonists), muscarine, VIP, forskolin and slow excitatory synaptic transmission all produced identical responses: an inward current associated with a membrane conductance decrease at the resting potential. The actions of any one occluded the actions of any other and all responses were pertussis‐toxin insensitive. 3. These agonists produced a voltage‐independent decrease in a ‘leak’ potassium conductance between ‐40 and ‐120 mV in 14% of neurones. 4. These agonists decreased a voltage‐dependent, calcium‐activated potassium conductance between ‐40 and ‐80 mV in all other (86%) neurones. The agonists still evoked an inward current without apparent conductance change at potentials between ‐90 and ‐130 mV. 5. In a low calcium solution containing cobalt or cadmium, the agonists produced an inward current associated with a conductance increase from ‐40 to ‐120 mV. Ion replacement studies indicated this current was due to an increase in a cation‐selective (mainly sodium) conductance. 6. The agonists also reduced the inwardly rectifying potassium current that is activated by somatostatin and alpha 2‐adrenoceptor agonists in these neurones. The agonists did not alter the inwardly rectifying potassium current that is present in these neurones in the absence of somatostatin or alpha 2‐agonists. 7. Thus, SP, 5‐HT, muscarine, VIP and the release of slow excitatory transmitters all appear to act through a common intracellular transduction pathway, an increase in adenylate cyclase. This results in an activation of a sodium‐selective cation current and an inhibition of three distinct potassium conductances: the background potassium conductance, the calcium‐activated potassium conductance and the inwardly rectifying potassium conductance activated by somatostatin and alpha 2‐adrenoceptor agonists.

Original languageEnglish (US)
Pages (from-to)483-501
Number of pages19
JournalThe Journal of Physiology
Volume462
Issue number1
DOIs
StatePublished - Mar 1 1993

ASJC Scopus subject areas

  • Physiology

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