Calcium currents are altered in the vascular muscle cell membrane of spontaneously hypertensive rats.

Abstract

Calcium currents were recorded during whole-cell voltage damp in cultured azygos venous muscle cells from 1-3-day-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Different holding potentials were used to separate total cell current into its transient (T) and sustained or long-lasting (L) components. In recordings from 30 WKY and 30 SHR vascular cells, total cell calcium current was the same between cells from normotensive (167±20 pA) and hypertensive (139±15 pA) rats. However, the relative proportion of T and L calcium currents was different between WKY and SHR cells. In WKY cells, the peak amplitude of the L current was less than that of the T current (42±30% of total current), whereas in SHR cells, the L current was greater (62±3% of total current). Calcium currents in vascular muscle cells from SHR were activated and inactivated at more positive potentials than in cells from WKY. This study directly compares transmembrane calcium current in isolated cells from WKY and SHR blood vessels and shows that the proportions of T and L calcium channels activated by depolarization are altered in this genetic model of hypertension. ). Cellular mechanisms of calcium metabolism reported to be associated with hypertension in the spontaneously hypertensive rat (SHR) include changes in intracellular release and reuptake of calcium and alterations in sarcolemmal transport of and permeability to the ion. 2 -6 The recent introduction of the tight-seal patchclamp technique 7 for the measurement of transmembrane calcium currents in vascular muscle cells 8 -13 enables the implementation of a powerful tool to directly compare the properties of voltage-dependent calcium channels in cells from normotensive and hypertensive animals. In the experiments described here, we used the whole-cell voltage-clamp technique 7 to measure calcium currents and compared the voltagedependent calcium channels in cultured vascular mus-

The control of Ca 2+ influx and NFATc3 signaling in arterial smooth muscle during hypertension

“…We also provide the first direct demonstration that PKC␣ contributes to the development of AngII-induced hypertension. We show that increased Ca 2ϩ influx during hypertension is not simply the result of random activation of LTCCs as previously implied (3,4). Rather, increased Ca 2ϩ influx during hypertension results primarily from increased PKC␣-dependent persistent Ca 2ϩ sparklet activity.…”

“…Although the etiology of arterial dysfunction during hypertension is unclear, multiple studies suggest that increased L-type Ca 2ϩ channel (LTCC) activity in arterial smooth muscle is a major contributor to this pathological change (3,4). However, the mechanisms and functional implications of increased Ca 2ϩ influx via LTCCs remain unclear.…”

“…Several lines of evidence suggest that they may be important in this process. (i) LTCC function is increased in hypertensive arterial smooth muscle (3,4). (ii) The vasoconstrictor angiotensin II (AngII), an activator of PKC, is a likely contributor to vascular dysfunction in human (9) and model hypertension (10).…”

Salt and hypertension--future directions.

“…Although vascular and endothelial cells are small and difficult to manage, some investigators have successfully applied whole-cell patchclamp technology to study them. 36 Single-channel patch-clamp techniques will be increasingly applied to the study of K + and Ca 2+ channels in cells of humans and animals. These techniques, when combined with biochemistry studies of intracellular signaling pathways, should provide important new data on both primary and secondary changes of vessel reactivity and maintenance of enhanced vascular tone in hypertension.…”

An approach to the explanation of cell membrane alteration in primary hypertension.

“…20 The latter phenomenon was also observed in plasma membranes of cardiomyocytes and adipocytes of SHR, 13 and an increase of intracellular exchangeable calcium was revealed in adipose tissue in both types of primary hypertension. 27 At the same time, decreased activity of the calmodulin-dependent component of calcium pump activity was revealed in erythrocytes 28 and platelets 29 of EH patients and in erythrocytes, 30 synaptosomes, 25 and cardiomyocytes 31 of SHR. These studies were followed up by the finding of increased cytoplasmic free calcium concentration in platelets of both EH patients 32 The relation between alterations of cell calcium homeostasis and abnormalities in the transport systems of univalent cations in the plasma membrane is not always sufficiently clear.…”