Biomedical subjects

M R Lauer

Publications and source records attributed to M R Lauer.

21 records · Page 2Linked to original sources

PubMed1992

Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes.

1. Endothelin is a vasoactive peptide released from vascular endothelial cells which has potent cardiac inotropic effects. We examined the effect of endothelin on the verapamil-sensitive Ca2+ current (ICa) in enzymatically dispersed rabbit ventricular myocytes. 2. Using the whole-cell voltage clamp technique with a standard dialysing pipette solution, the application of extracellular endothelin (20 nM) did not increase the peak ICa, but in fact caused a small reversible decline (903 +/- 109 pA without endothelin, 727 +/- 95 pA with endothelin (means +/- S.E.M., n = 14, P less than 0.05)). 3. If GTP (100 microM) was added to the pipette solution, the extracellular application of endothelin (0.2 or 20 nM) caused a large, reproducible increase in peak ICa (871 +/- 85 pA without endothelin, 1230 +/- 110 pA with 20 nM-endothelin (n = 10, P less than 0.05). The endothelin enhancement of ICa occurred after a delay of approximately 3-4 min at room temperature. 4. The GTP requirement for the endothelin effect on ICa suggests that its effect may be mediated through a G protein-dependent pathway. To investigate this further, experiments were performed with pipette solutions containing guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), a GDP analogue which inhibits G protein cycling. With the addition of GDP beta S (0.5-5.0 mM) to the pipette solution (along with 100 microM-GTP), the effect of endothelin on peak ICa was blocked (1062 +/- 86 pA without endothelin, 1170 +/- 134 pA with endothelin (n = 11, P greater than 0.05)). 5. Incubation of myocytes with pertussis toxin (500 ng/ml) prevented the partial ACh-induced reversal of the isoprenolol enhancement of ICa. However, this identical treatment failed to block the endothelin enhancement of the voltage-dependent Ca2+ current (n = 4). 6. Taken together, these results confirm that while the effect of endothelin in rabbit cardiac ventricular myocytes is mediated through a G protein-dependent pathway, the G protein involved is pertussis toxin-insensitive.

Acetylcholine↗

PubMed1986

Altered Ca2+ dependence of tension development in skinned skeletal muscle fibers following modification of troponin by partial substitution with cardiac troponin C.

Binding of Ca2+ to the troponin C (TnC) subunit of troponin is necessary for tension development in skeletal and cardiac muscles. Tension was measured in skinned fibers from rabbit skeletal muscle at various [Ca2+] before and after partial substitution of skeletal TnC with cardiac TnC. Following substitution, the tension-pCa relationship was altered in a manner consistent with the differences in the number of low-affinity Ca2+-binding sites on the two types of TnC and their affinities for Ca2+. The alterations in the tension-pCa relationship were for the most part reversed by reextraction of cardiac TnC and readdition of skeletal TnC into the fiber segments. These findings indicate that the type of TnC present plays an important role in determining the Ca2+ dependence of tension development in striated muscle.

Animals↗

PubMed1984

H+-induced membrane depolarization in canine cardiac Purkinje fibers.

The H+-induced membrane depolarization in canine cardiac Purkinje cells in false tendons was studied. In some electrically paced Purkinje cells ("sensitive" cells), exposure to a pH 6.0 superfusate produced a large membrane depolarization [44.5 +/- 6.7 (SD) mV], whereas other Purkinje cells ("resistant" cells) developed only a small depolarization (9.8 +/- 5.6 mV) even after 60 min of exposure to the low-pH superfusate. Cs+, Ba2+, tetraethylammonium, 9-aminoacridine, verapamil, or exposure to Ca2+- or K+-deficient or hypertonic solutions were capable of converting resistant cells to sensitive cells. Increasing extracellular K+ concentration [( K+]) or rapid electrical pacing failed to convert resistant cells to sensitive cells. Membrane depolarizations of approximately equal magnitude produced in Purkinje cells by either increasing [K+] to 18.2 mM, decreasing [K+] to 0.5 mM, reducing extracellular pH to 4.1, or ouabain administration were associated with membrane resistances of approximately 45, 377, 386, or 45%, respectively, of the membrane resistances in the control solution. The results suggest that the H+-induced membrane depolarization in sensitive Purkinje cells is caused by a mechanism similar to that responsible for a low [K+]-induced depolarization.

Aminacrine↗