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Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents.
Cardiovasc Res. 2006 Apr 01; 70(1):88-96.CR

Abstract

OBJECTIVE

Sphingosine-1-phosphate (S-1-P), a potent lysophospholipid mediator which is released from platelets during clotting, activates a G-protein-gated inwardly rectifying K+ current (GIRK) in atrial and sino-atrial node myocytes. We denote this current I(K(S-1-P).) A similar GIRK, which is activated by acetylcholine (ACh) and denoted I(K(ACh)), is expressed in atrium. It shortens the action potential duration (APD) and reduces the effective refractory period (ERP). We have examined the effect of S-1-P on APD in guinea pig atrial myocytes by characterizing the rectification properties of I(K(S-1-P)) and evaluating whether I(K(S-1-P)) and I(K(ACh)) exhibit convergence/occlusion.

METHODS

Membrane potential and K+ currents were recorded from guinea pig atrial myocytes. Inwardly rectifying K+ currents were recorded using a ramp voltage clamp waveform between +30 to -130 mV from a holding potential of -7 mV. Agonist-induced current changes were obtained by subtracting the control current.

RESULTS

S-1-P (1 and 10 nM) altered both passive and active properties of atrial myocytes. S-1-P increased the threshold current for excitation and decreased the time constant of the subthreshold electrotonic potentials. In addition, both APD50 and APD90 were decreased substantially. Voltage clamp analysis showed that the outward conductance of I(K(IR)) (G(K(IR)out)) was 134.8+/-11.3 pS pF(-1) (n = 19) in S-1-P (100 nM), and 207.0+/-19.6 pS pF(-1) (n = 18) in ACh (10 microM). The ratio of G(K(IR)out):G(K(IR)in) was about 0.7 for both S-1-P and ACh. The EC50 values for the activation of G(K(IR)out) and G(K(IR)in) by S-1-P were 1.6 and 1.3 nM, respectively. Addition of S-1-P (100 nM) after the effect of ACh (10 microM) had developed fully caused very little additional change.

CONCLUSION

I(K(S-1-P)) is carried by weakly inwardly-rectifying K+ channels that are the same as those activated by ACh. This K+ current can markedly shorten APD in guinea pig atrial myocytes. This effect would be expected to increase the incidence of atrial rhythm disturbances.

Authors+Show Affiliations

Ochi R
Department of Bioengineering and Medicine, University of California San Diego, La Jolla, California 92093-0412, USA.
Momose Y
No affiliation info available
Oyama K
No affiliation info available
Giles WR
No affiliation info available

MeSH

AcetylcholineAction PotentialsAdenosine DiphosphateAnimalsDose-Response Relationship, DrugGuinea PigsHeart AtriaLysophospholipidsMembrane PotentialsMyocytes, CardiacPatch-Clamp TechniquesPotassium Channels, Inwardly RectifyingSphingosineStimulation, Chemical

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16545787

Citation

Ochi, Rikuo, et al. "Sphingosine-1-phosphate Effects On Guinea Pig Atrial Myocytes: Alterations in Action Potentials and K+ Currents." Cardiovascular Research, vol. 70, no. 1, 2006, pp. 88-96.
Ochi R, Momose Y, Oyama K, et al. Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents. Cardiovasc Res. 2006;70(1):88-96.
Ochi, R., Momose, Y., Oyama, K., & Giles, W. R. (2006). Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents. Cardiovascular Research, 70(1), 88-96.
Ochi R, et al. Sphingosine-1-phosphate Effects On Guinea Pig Atrial Myocytes: Alterations in Action Potentials and K+ Currents. Cardiovasc Res. 2006 Apr 1;70(1):88-96. PubMed PMID: 16545787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents. AU - Ochi,Rikuo, AU - Momose,Yasunori, AU - Oyama,Kosuke, AU - Giles,Wayne R, Y1 - 2006/03/20/ PY - 2005/08/23/received PY - 2005/12/30/revised PY - 2006/01/10/accepted PY - 2006/3/21/pubmed PY - 2006/8/23/medline PY - 2006/3/21/entrez SP - 88 EP - 96 JF - Cardiovascular research JO - Cardiovasc Res VL - 70 IS - 1 N2 - OBJECTIVE: Sphingosine-1-phosphate (S-1-P), a potent lysophospholipid mediator which is released from platelets during clotting, activates a G-protein-gated inwardly rectifying K+ current (GIRK) in atrial and sino-atrial node myocytes. We denote this current I(K(S-1-P).) A similar GIRK, which is activated by acetylcholine (ACh) and denoted I(K(ACh)), is expressed in atrium. It shortens the action potential duration (APD) and reduces the effective refractory period (ERP). We have examined the effect of S-1-P on APD in guinea pig atrial myocytes by characterizing the rectification properties of I(K(S-1-P)) and evaluating whether I(K(S-1-P)) and I(K(ACh)) exhibit convergence/occlusion. METHODS: Membrane potential and K+ currents were recorded from guinea pig atrial myocytes. Inwardly rectifying K+ currents were recorded using a ramp voltage clamp waveform between +30 to -130 mV from a holding potential of -7 mV. Agonist-induced current changes were obtained by subtracting the control current. RESULTS: S-1-P (1 and 10 nM) altered both passive and active properties of atrial myocytes. S-1-P increased the threshold current for excitation and decreased the time constant of the subthreshold electrotonic potentials. In addition, both APD50 and APD90 were decreased substantially. Voltage clamp analysis showed that the outward conductance of I(K(IR)) (G(K(IR)out)) was 134.8+/-11.3 pS pF(-1) (n = 19) in S-1-P (100 nM), and 207.0+/-19.6 pS pF(-1) (n = 18) in ACh (10 microM). The ratio of G(K(IR)out):G(K(IR)in) was about 0.7 for both S-1-P and ACh. The EC50 values for the activation of G(K(IR)out) and G(K(IR)in) by S-1-P were 1.6 and 1.3 nM, respectively. Addition of S-1-P (100 nM) after the effect of ACh (10 microM) had developed fully caused very little additional change. CONCLUSION: I(K(S-1-P)) is carried by weakly inwardly-rectifying K+ channels that are the same as those activated by ACh. This K+ current can markedly shorten APD in guinea pig atrial myocytes. This effect would be expected to increase the incidence of atrial rhythm disturbances. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/16545787/Sphingosine_1_phosphate_effects_on_guinea_pig_atrial_myocytes:_Alterations_in_action_potentials_and_K+_currents_ DB - PRIME DP - Unbound Medicine ER -