RESUMEN
The role gap junction channels play in the normal and abnormal functioning of the vascular wall is the subject of much research. The biophysical properties of gap junctions are an essential component in understanding how gap junctions function to allow coordinated relaxation and contraction of vascular smooth muscle. This study reviews the properties thus far elucidated and relates those properties to tissue function. We ask how biophysical and structural properties such as gating, permselectivity, subconductive states and channel type (heteromeric vs homotypic vs heterotypic) might affect vascular smooth muscle tone.
Asunto(s)
Conexinas/fisiología , Uniones Comunicantes/fisiología , Músculo Liso Vascular/fisiología , Fenómenos Biofísicos , Biofisica , Conexinas/metabolismo , Uniones Comunicantes/metabolismo , Humanos , Tono Muscular , Músculo Liso Vascular/química , Músculo Liso Vascular/citologíaRESUMEN
Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of alpha1-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal ( approximately 75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 microM), prostaglandin F2alpha (PGF2alpha; 1 microM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 microM and 500 microM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 +/- 6% (N = 26 rings) to 57 +/- 7% (N = 26 rings) and 34.9 +/- 6% (N = 13 rings), respectively (P<0.05), and for PGF2alpha from a control response of 75 +/- 10% (N = 16 rings) to 52 +/- 8% (N = 19 rings) and 25.9 +/- 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 microM and 500 microM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 +/- 5. 0% for the control response (N = 38 rings), 59 +/- 6.0% in the presence of 200 microM heptanol (N = 17 rings), and 70 +/- 6.0% in the presence of 500 microM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 +/- 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.