dihydropyridines and Muscular-Diseases

We report a 46-year-old man with primary aldosteronism presenting hypokalemia, periodic paralysis and hypokalemic myopathy whose clinical course paralleled with the dosage of benidipine hydrochloride, a dihydropyridine calcium channel blocker (DHP-CCB), administered for the treatment of hypertension. To see relations between DHP-CCB and episodes of motor weakness in patients with primary aldosteronism, we surveyed retrospectively the history of motor weakness and anti-hypertensive drugs in 14 consecutive cases with primary aldosteronism in our institute. Five patients out of 11 cases (45.5%) who had received DHP-CCB experienced muscle weakness, however, the rest of three patients receiving other anti-hypertensive drug had not experienced weakness. Though, less attention has been paid as thiazide diuretics, it is reported that DHP-CCB also induces hypokalemia through several mechanisms. However, the occurrence of motor weakness by DHP-CCB is very rare. Our results show that primary aldosteronism should be taken into account when we encounter patients manifesting episodic motor weakness by the use of DHP-CCB.

Topics: Calcium Channel Blockers; Dihydropyridines; Humans; Hyperaldosteronism; Hypokalemia; Hypokalemic Periodic Paralysis; Male; Middle Aged; Muscular Diseases

Topics: Action Potentials; Animals; Caffeine; Calcium; Calcium Channels; CHO Cells; Cricetinae; Dihydropyridines; Genes; Humans; Malignant Hyperthermia; Mammals; Mice; Mice, Mutant Strains; Muscle Contraction; Muscle Proteins; Muscular Diseases; Myocardial Contraction; Organ Specificity; Protein Engineering; Receptors, Nicotinic; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Signal Transduction

A human clone corresponding to the gene encoding the alpha 1 subunit of the cardiac dihydropyridine-sensitive calcium channel (CCHL1A1) has been isolated and partially sequenced. Oligonucleotides based on the human sequence were constructed and used in the polymerase chain reaction to amplify specifically this human gene in human-rodent somatic cell hybrids. Using somatic cell hybrids that contained defined regions of human chromosome 12, the human alpha 1 subunit of the cardiac dihydropyridine-sensitive calcium channel has been assigned to the short arm of chromosome 12 in the interval 12p12-pter.

Topics: Amino Acid Sequence; Animals; Base Sequence; Calcium Channels; Chromosome Mapping; Chromosomes, Human, Pair 12; Cricetinae; Cricetulus; Dihydropyridines; Genes; Genes, Lethal; Humans; Hybrid Cells; Mice; Mice, Mutant Strains; Molecular Sequence Data; Muscular Diseases; Myocardium; Polymerase Chain Reaction; Rabbits; Sequence Homology, Nucleic Acid; Species Specificity

There are dihydropyridine (DHP)-sensitive calcium currents in both skeletal and cardiac muscle cells, although the properties of these currents are very different in the two cell types (for simplicity, we refer to currents in both tissues as L-type). The mechanisms of depolarization-contraction coupling also differ. As the predominant voltage-dependent calcium current of cardiac cells, the L-type current represents a major pathway for entry of extracellular calcium. This entry triggers the subsequent large release of calcium from the sarcoplasmic reticulum (SR). In contrast, depolarization of skeletal muscle releases calcium from the SR without the requirement for entry of extracellular calcium through L-type calcium channels. To investigate the molecular basis for these differences in calcium currents and in excitation-contraction (E-C) coupling, we expressed complementary DNAs for the DHP receptors from skeletal and cardiac muscle in dysgenic skeletal muscle. We compared the properties of the L-type channels produced and showed that expression of a cardiac calcium channel in skeletal muscle cells results in E-C coupling resembling that of cardiac muscle.

Topics: Animals; Calcium; Calcium Channels; Dihydropyridines; DNA; Electrophysiology; Mice; Muscle Contraction; Muscles; Muscular Diseases; Myocardial Contraction; Myocardium; Receptors, Nicotinic; Sarcoplasmic Reticulum; Transfection

The different membrane systems and proteins involved in the control of intracellular calcium movements in the skeletal muscle cell are described. These include the sarcoplasmic reticulum, that Ca(++)-ATPase sarcoplasmic reticular calcium pump, transverse tubules, calcium channels, and the ryanodine receptor protein. The significance of these systems is shown clearly in the myopathies, where the main errors involved do not concern the contractile system, but the command and control mechanisms.

Topics: Calcium; Calcium Channels; Calcium-Transporting ATPases; Dihydropyridines; Humans; Muscle Contraction; Muscles; Muscular Diseases; Myofibrils; Receptors, Cell Surface; Ryanodine; Sarcoplasmic Reticulum

Microinjection of an expression plasmid that carries complementary DNA encoding the receptor for dihydropyridine calcium channel blockers of skeletal muscle restores both excitation-contraction coupling and slow calcium current in cultured skeletal muscle cells from mice with muscular dysgenesis. This suggests that the dihydropyridine receptor in the transverse tubule membrane of skeletal muscle functions both as the voltage sensor for excitation-contraction coupling and as the slow calcium channel.

Topics: Animals; Calcium; Cells, Cultured; Dihydropyridines; DNA; Mice; Muscle Contraction; Muscular Diseases; Mutation; Polymorphism, Restriction Fragment Length