Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

Abstract

While subtypes 1 and 2 of the ryanodine receptor (RyR) function as intracellular Ca2+ release channels, little is known about the function of the third subtype (RyR-3), first identified in brain. Myocytes from mice homozygous for a targeted mutation in the RyR-1 gene (dyspedic mice) can now be used for a study on the function of RyR-3, which is predominantly expressed in these cells according to our reverse transcriptionpolymerase chain reaction analysis. We here demonstrate in these myocytes caffeine-, ryanodine-and adenine nucleotide-sensitive Ca>+-induced Ca2> release with -10 times lower sensitivity to Ca2+ than that of RyR-1. Although RyR-3 does not mediate excitationcontraction coupling of the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+ release in response to a Ca2+ rise with a high threshold.

Similar Ca2+ dependences of [3H]ryanodine binding to α‐ and β‐ryanodine receptors purified from bullfrog skeletal muscle in an isotonic medium

“…The modulation of CICR by component(s) other than RyR could also be considered as a reasonable explanation. In this connection, it is noted that CICR in the dispedic mice was also less sensitive to adenine nucleotide or caffeine [26].…”

“…In mammalian skeletal muscles, Ryrl functions as the DICR channel, because skeletal muscles of ryrl-targeted mice (dispedic mice) fail to show DICR from SR [26]. Recently, mRNA for Ryr3 has been detected in mammalian skeletal muscles [26,27].…”

“…Recently, mRNA for Ryr3 has been detected in mammalian skeletal muscles [26,27]. However, the amount of the isoform is considered to be very minute, because only a single band corresponding to Ryrl is visible on SDS-PAGE of SR vesicles from these muscles in contrast to two bands which are observed in SR vesicles from bullfrog skeletal muscle.…”

“…However, the amount of the isoform is considered to be very minute, because only a single band corresponding to Ryrl is visible on SDS-PAGE of SR vesicles from these muscles in contrast to two bands which are observed in SR vesicles from bullfrog skeletal muscle. Takeshima et al [26] reported that the CICR activity in the dispedic mice in which mRNA for Ryr3 was detected was about 10 times less sensitive to Ca 2+ than that in the control mice. One possible reason for the different result might be the difference in species.…”

Type 1 and type 3 ryanodine receptors are selectively involved in muscarinic antinociception in mice: An antisense study

“…The knockdown of RyR subtypes by administration of aODNs was necessary since mice missing the RyR1 and RyR2 gene products die early during embryonic development. Mice carrying a targeted disruption of the RyR1 gene show complete loss of the skeletal muscle excitation-contraction coupling and die perinatally due to respiratory failure (Takeshima et al, 1995). Similarly to that observed in RyR1 knockout mice, generation of mice carrying a targeted disruption of the RyR2 gene indicates a pivotal role of this isoform not only in cardiac excitation-contraction coupling, but also during myocardial development, as RyR2 knockout mice die at embryonic day 10 and show morphological abnormalities in the heart tube (Takeshima et al, 1998).…”