PHOSPHOLAMBAN DEFICIENCY ALTERS INACTIVATION KINETICS OF L-TYPE CA2+ CHANNELS IN MOUSE VENTRICULAR MYOCYTES

Entry of Ca2+ through voltage-dependent L-type Ca2+ channels is critic al for contraction in cardiac cells. In recent studies, cells from pho spholamban (PLB) knockout (PLB-KO) mouse hearts showed significantly i ncreased basal contractility with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake. To test whether these effects of PLB ablation were assoc iated with alterations of L-type Ca2+ channel function, we compared th e properties of Ca2+ channel currents (I-Ca) in ventricular myocytes i solated from wild-type (WT) and PLB-KO mouse hearts. L-type Ca2+ chann els from mouse myocytes exhibited voltage-dependent gating and sensiti vity to dihydropyridine drugs, similar to other mammalian species, and these properties were not altered by PLB ablation. I-Ca from both WT and PLB-KO cells revealed two (fast and slow) components of inactivati on kinetics. However, the proportion of the faster component was signi ficantly larger in PLB-KO cells. Ryanodine (10 mu M) reduced the rate of inactivation of I-Ca for both WT and PLB-KO cells, but the reductio n was more prominent in PLB-KO cells compared with WT cells. In contra st, the inactivation in a Ba2+ solution could be fitted by a single ex ponential similar to the slower component in Ca2+, and this was not al tered in PLB-KO cells. The increase in the fast Ca2+-dependent inactiv ation component in PLB-KO cells supports the hypothesis that Ca2+ rele ased from the SR regulates Ca2+ channel inactivation by affecting the levels of Ca2+ near the channel and suggests that this may be an impor tant compensatory mechanism in the hyperdynamic PLB-KO heart.