Carbachol-induced sodium current in guinea pig ventricular myocytes is not regulated by guanine nucleotides.

Abstract

Muscarinic (M2) receptor occupancy by carbachol induces a tetrodotoxin- and pertussis toxin-resistant Na+ current which underlies its positive inotropic effect in guinea pig ventricular cells. We tested the effect of activating [GTP gamma S, Gpp(NH)p] and inactivating (GDP beta S) guanine nucleotides on this carbachol-induced current because guanine nucleotide binding proteins are reported to transduce the effect of muscarinic agonist. A whole-cell voltage clamp method was used. The carbachol (300 microM)-induced current was not significantly changed at any membrane voltage in the absence and the presence of 10 microM GTP gamma S, 100 microM Gpp(NH)p or 500 microM GDP beta S in the patch pipette (inward current amplitude at -80 mV: -21 +/- 1.5 pA, control; -22 +/- 1.3 pA, GTP gamma S; -20, -16 pA, Gpp(NH)p; -20 +/- 2.3 pA, GDP beta S; n = 31, 11, 2 and 14, respectively). The current amplitude was not affected by prolonged dialysis (120 min) of the cell with Gpp(NH)p and/or by the presence of greater concentrations of guanine nucleotides. On the other hand, 10 microM GTP gamma S directly activated the muscarinic K+ channel current within 60 sec after patch rupture in atrial myocytes; either GTP gamma S or GDP beta S (500 microM) occluded activation of this current by carbachol. When isoproterenol had increased L-type Ca++ current in ventricular myocytes, carbachol-induced inhibition of this current was suppressed when GTP gamma S (10 microM) was present in the pipette solution. Therefore, myocytes were dialyzed with effective concentrations of guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: T Shirayama, K Matsumoto, A J Pappano
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 265 Issue 2 Pg. 641-8 (May 1993) ISSN: 0022-3565 [Print] United States
• PMID: 8388456 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Guanine Nucleotides
• Receptors, Muscarinic
• Sodium Channels
• Carbachol

Topics

• Animals
• Carbachol (pharmacology)
• Dialysis
• Guanine Nucleotides (metabolism)
• Guinea Pigs
• Heart Ventricles (cytology, drug effects)
• In Vitro Techniques
• Membrane Potentials
• Receptors, Muscarinic (drug effects, metabolism)
• Signal Transduction
• Sodium Channels (drug effects, physiology)
• Ventricular Function