Agonist-independent modulation of L-type Ca currents by basal Gs protein activities in single guinea pig ventricular myocytes

Toshinori Makita, Minoru Horie, Lai Hua Xie, Yasunobu Okada, Shigetake Sasayama

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The modulation of L-type Ca2+ currents (ICa, L) by the basal activities of G proteins was studied in adult guinea pig ventricular myocytes by whole-cell patch-clamp techniques. With intrapipette guanosine triphosphate (GTP) (100μM), a specific inhibition of Gi proteins by pertussis toxin (PTX) produced an increase in the basal density of ICa, L (from 11.0 ± 0.8, n = 13, to 25.0 ± 2.0pA/pF, n = 11, at 0mV test potential). In addition, PTX shifted the forskolin (Fsk) concentration-ICa, L response relation significantly leftward (EC50 = 63.7 ± 12.5 vs 625 ± 75nM). With intrapipette guanosine diphosphate (GDP)βS (1mM), the Fsk-ICa, L relation was also shifted leftward (EC50 = 197 ± 18.3 vs 781 ± 82.5 nM). However, chronic GDPβS dialysis accelerated the rundown of ICa, L significantly, suggesting a potential contribution of GS proteins in maintaining basal ICaL. In contrast, intra-pipette GTPγS (100μM) produced a transient rise in ICa, L from 11.0 ± 3.0 to 22.8 ± 7.0 pA/pF (in 3.4 min after whole-cell formation at 0mV, n = 9), presumably through the activation of GS proteins. It was followed by a gradual decline in ICa, L (to 15.5 ± 3.5 pA/pF), which was still enhanced by Fsk (EC50 = 1450 ± 98nM), indicating that the current decay was not solely due to rundown but to activation of Gi proteins. GS, in addition to Gi proteins, show sufficient basal activity to modulate ICa, L in an agonist-independent manner.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
JournalHeart and Vessels
Volume15
Issue number5
DOIs
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Keywords

  • Adrenergic agonist
  • Ca channel
  • G protein
  • Muscarinic agonist
  • Receptor

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