Effect of isoprenaline on Ca2+ channel current in single smooth muscle cells isolated from taenia of the guinea-pig caecum.

Abstract

1. The effects of isoprenaline (Iso) on Ca2+ channel current in enzymatically isolated single cells of the guinea-pig taenia caeci were examined using the standard whole-cell voltage-clamp method. 2. Iso potentiated the voltage-dependent Ca2+ current; the threshold and maximally effective concentration of Iso to increase Ca2+ current were 3-10 nM and 1-3 microM, respectively. The average increase in Ca2+ current produced by 3 microM Iso was 42 +/- 6% (mean +/- S.E.M.) and the response could be obtained repeatedly in the same cell. The concentration-response relationship could be fitted by a binding model with a Hill coefficient of 1 and a dissociation constant of 42 nM. 3. The effect of Iso on Ca2+ current was voltage dependent. Although potentiation of Ca2+ current by Iso was obvious between -30 and +10 mV, it was small or absent around +20 to +30 mV. Iso had little effect on the relationship between inactivation of the Ca2+ current and voltage obtained using a double-pulse protocol. 4. External application of forskolin, an adenylyl cyclase activator, or internal perfusion of cAMP or dibutyryl cAMP from the recording pipette, did not increase Ca2+ current and potentiation of Ca2+ current by Iso was observed repeatedly and was unchanged. 5. Internal perfusion of GTP gamma S or GDP beta S increased or did not affect the Ca2+ current and potentiation of Ca2+ current by Iso was unchanged and could be recorded repeatedly for about 20 min after rupture of the cell membrane. In addition, treatment of cells with the potent protein kinase C inhibitor, chelerythrine, had no effect on Ca2+ current or on potentiation of Ca2+ current by Iso. 6. These results suggest that the Ca2+ current in guinea-pig taenia caeci cells is potentiated by isoprenaline via mechanisms which do not involve either a cAMP pathway, a G-protein pathway or a protein kinase C pathway. The receptor involved appeared to be an atypical adrenoreceptor not blocked by either alpha- or beta-receptor blocking agents.

• Authors: K Muraki, T B Bolton, Y Imaizumi, M Watanabe
• Journal: The Journal of physiology (J Physiol) Vol. 471 Pg. 563-82 (Nov 1993) ISSN: 0022-3751 [Print] England
• PMID: 8120822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• Receptors, Adrenergic
• Thionucleotides
• Guanosine Diphosphate
• Guanosine 5'-O-(3-Thiotriphosphate)
• guanosine 5'-O-(2-thiodiphosphate)
• Cyclic AMP
• GTP-Binding Proteins
• Isoproterenol

Topics

• Animals
• Calcium Channels (drug effects, metabolism)
• Cecum (metabolism)
• Cyclic AMP (metabolism)
• Female
• GTP-Binding Proteins (metabolism)
• Guanosine 5'-O-(3-Thiotriphosphate) (pharmacology)
• Guanosine Diphosphate (analogs & derivatives, pharmacology)
• Guinea Pigs
• In Vitro Techniques
• Isoproterenol (pharmacology)
• Kinetics
• Male
• Membrane Potentials (physiology)
• Muscle, Smooth (cytology, drug effects, metabolism)
• Receptors, Adrenergic (drug effects, physiology)
• Thionucleotides (pharmacology)