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

Ke-Zhong Shen, A. Surprenant

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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. 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. These agonists produced a dent decrease in a 'leak' potassium conductance between -40 and -120 mV in 14% of neurones. 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. 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. The agonists also reduced the inwardly rectifying potassium current that is activated by somatostatin and α2-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 α2-agonists. 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 α2-adrenoceptor agonists.

Original languageEnglish (US)
Pages (from-to)483-501
Number of pages19
JournalJournal of Physiology
Volume462
StatePublished - 1993

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Substance P
Potassium
Guinea Pigs
Neurons
Muscarine
Vasoactive Intestinal Peptide
Somatostatin
Serotonin
Colforsin
Calcium
Adrenergic Receptors
Cations
Sodium
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Membranes
Pertussis Toxin
Cobalt
Cadmium
Adenylyl Cyclases

ASJC Scopus subject areas

  • Physiology

Cite this

Common ionic mechanisms of excitation by substance P and other transmitters in guinea-pig submucosal neurones. / Shen, Ke-Zhong; Surprenant, A.

In: Journal of Physiology, Vol. 462, 1993, p. 483-501.

Research output: Contribution to journalArticle

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